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PUFA Increases Estrogen

Also see:
PUFA Inhibit Glucuronidation
PUFA, Estrogen, Obesity and Early Onset of Puberty

Quotes by Ray Peat, PhD:
“The pro-estrogenic nature of the unsaturated fatty acids is probably the biggest barrier to the radical elimination of degenerative diseases. Various saturated fatty acids, including butyric, octanoic, and palmitic, have protective effects on mitochondrial respiration.”

“Two ubiquitous carcinogenic factors that can be manipulated without toxins are the polyunsaturated fatty acids (PUFA) and estrogen. These closely interact with each other, and there are many ways in which they can be modulated.”

“The unsaturated fatty acids, but not the saturated fatty acids, free estrogen from the serum proteins that bind it, and increase its availability and activity in tissue cells.”

“While the competition by PUFA for protein binding sites block the effects of thyroid hormone and vitamin A, the actions of PUFA on sex steroid binding protein (SBP, or SSBG, for sex steroid binding globulin) increases the activity of estrogen. That’s because the SSBG neutralizes estrogen by binding to it, keeping it out of cells; free PUFA keep it from binding estrogen (Reed, et al.).”

J Steroid Biochem. 1986 Feb;24(2):657-9.
Free fatty acids: a possible regulator of the available oestradiol fractions in plasma.
Reed MJ, Beranek PA, Cheng RW, James VH.
Consumption of dietary fats has been linked to the high incidence of breast cancer found in Western women. In vitro studies we have carried out show that unsaturated free fatty acids can increase the biologically available oestradiol fractions in plasma. It is possible therefore that the increased risk for breast cancer associated with a diet high in fats may be related to an elevation in the biologically available oestradiol fractions in plasma.

Ann N Y Acad Sci. 1988;538:257-64.
Possible relevance of steroid availability and breast cancer.
Bruning PF, Bonfrer JM.
The as yet circumstantial evidence for a central role of estrogens in the promotion of human breast cancer is supported by many data. However, it has not been possible to identify breast cancer patients or women at risk by abnormally elevated estrogen levels in plasma. The concept of available, i.e., non-SHBG bound sex steroid seems to offer a better understanding than total serum steroid levels do. We demonstrated that sex steroid protein binding is decreased by free fatty acids. This finding may help to explain how the affluent Western diet and sedentary life style is related to high incidence rates of breast cancer. We have postulated that it is especially the central (abdominal) type of obesity which may increase sex steroid availability. This mechanism could be important already at the age of breast development when the sensitivity to promotion seems relatively great. It may also explain the increased incidence rates which are observed in Western industrialized countries after menopause. It seems likely that other endocrine-related cancer, such as endometrial or prostatic carcinomas are influenced in an analogous way.

Prostaglandins Leukot Essent Fatty Acids. 1993 Jan;48(1):111-6.
The role of free fatty acids in regulating the tissue availability and synthesis of sex steroids.
Reed MJ, Dunkley SA, Singh A, Thomas BS, Haines AP, Cruickshank JK.
Sex steroids and dietary fat intake have been implicated in the growth of breast tumours. We have previously shown that the plasma free oestradiol fraction is increased in women with breast cancer and that the addition of free fatty acids (FFA) to plasma can increase the free oestradiol fraction in vitro. In the present study we have examined the distribution of oestradiol and testosterone in serum obtained from European women (EW) and Asian (Gujarati) women (GW) living in north-west London. Fat intake by these women is similar but GW, who are vegetarians, consume a greater proportion of unsaturated fats. In serum from perimenopausal GW, the free testosterone concentration was significantly higher than for EW (11.1 +/- 3.6 pmol/l vs 8.7 +/- 3.4 pmol/l, p < 0.05). Although a significant correlation was found between the free testosterone and FFA concentrations for GW (r = 0.49, p < 0.05), concentrations of sex-hormone binding globulin (SHBG) were significantly lower in GW than EW. The finding of lower SHBG concentration in GW was confirmed in a second study in postmenopausal women (EW, 60.1 +/- 34.1 nmol/l; GW, 37.8 +/- 20.5 nmol/l, p < 0.05). However, no difference in the free oestradiol fraction or concentration was detected for EW and GW and no correlations with total or individual FFA were found. It is concluded from this study that while dietary fats may have an important role in the development of breast tumours, it is unlikely to be mediated by FFA inhibiting the binding of sex steroids to plasma proteins.

Another interesting association of the highly unsaturated fats and estrogen in relation to brain function is that DHA increases the entry of estrogen into the pregnant uterus, but inhibits the entry or progesterone (Benassayag, et al., 1999) which is crucual for brain cell growth. – Ray Peat, PhD

Prostaglandins Leukot Essent Fatty Acids. 1999 May-Jun;60(5-6):393-9.
Does high polyunsaturated free fatty acid level at the feto-maternal interface alter steroid hormone message during pregnancy?
Benassayag C, Rigourd V, Mignot TM, Hassid J, Leroy MJ, Robert B, Civel C, Grangé G, Dallot E, Tanguy J, Nunez EA, Ferré F.
Polyunsaturated fatty acids (PUFA) are important in pregnancy, fetal development and parturition. We measured free fatty acids (FFA), albumin and alpha-fetoprotein (AFP) in the maternal and fetal circulations of women undergoing elective Caesarean section at term. We also studied the impact of PUFAs on estrogen (ER) and progesterone receptors (PR) binding properties in vitro in the myometria of pregnant women and ex vivo in human myometrial cells in culture. FFA in intervillous blood (I) (feto-maternal interface) and maternal peripheral blood (M) were similar, while those in the umbilical vein (V) and arteries (A) were 2-4 fold lower (P<0.001). PUFA levels were low in M and 3 fold higher in I, A and V (P< 0.001); consequently C20:4 and C22:6 were most abundant in intervillous space. Albumin was uniformly distributed throughout the maternal-fetal unit, but there was a transplacental gradient in AFP. The AFP in the intervillous space had a special conformation (less immuno-reactive, more anionic), suggesting loading with PUFA. Physiological concentrations of C20:4 stimulated estradiol binding, but inhibited progestin binding. C20:4 inhibited progesterone binding by decreasing the number of binding sites, with no change in apparent affinity, in vitro in myometrial tissue and ex vivo in myometrial cells. Thus PUFA may modulate the steroid hormone message, so that the high C20:4 concentration at the maternal-fetal interface at term may help amplify the estrogen signal and inhibit the progesterone signal.

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By Team FPS – February 22, 2012

Long Chain Fats Decrease Insulin Metabolism

Endocrinology. 2003 Jun;144(6):2404-8.
In vitro inhibition of insulin-degrading enzyme by long-chain fatty acids and their coenzyme A thioesters.
Hamel FG, Upward JL, Bennett RG.
Insulin-degrading enzyme is responsible for initiating insulin degradation in cells, but little is known about the factors controlling its activity. Because obesity and high levels of free fatty acids decrease insulin clearance, we examined the effect of some common free fatty acids and their acyl-coenzyme A thioesters on insulin-degrading enzyme partially purified from the livers of male Sprague Dawley rats. Octanoic acid (C8:0) had no effect on activity. Long-chain free fatty acids (C16-C20) inhibited between 50% and 90% of the insulin degradation with IC(50) values in the range of 10-50 micro M. In general, the corresponding acyl-coenzyme A thioesters had lower IC(50) values and were slightly more efficacious. (125)I-insulin cross-linking studies showed free fatty acids did not inhibit hormone binding to insulin-degrading enzyme. Kinetic analysis showed a noncompetitive type of inhibition. Furthermore, fatty acids eliminated the ability of insulin to inhibit the proteasome. These results suggest that when intracellular long-chain fatty acid concentrations are elevated, they may act directly on insulin-degrading enzyme to decrease insulin metabolism and alter insulin action in intact cells. This mechanism may contribute to the hyperinsulinemia and insulin resistance seen with elevated fatty acids and obesity.

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By Team FPS – February 21, 2012

Fish – Elongase and Desaturase Enzymes

Aquaculture Volume 290, Issues 1–2, 4 May 2009, Pages 122–131
Physiological roles of fatty acyl desaturases and elongases in marine fish: Characterisation of cDNAs of fatty acyl Δ6 desaturase and elovl5 elongase of cobia (Rachycentron canadum)
Xiaozhong Zheng, Zhaokun Ding, Youqing Xu, Oscar Monroig, Sofia Morais, Douglas R. Tocher
In the present paper, we investigated the expression of fatty acyl desaturase and elongase genes in a marine teleost, cobia, a species of great interest due to its considerable aquaculture potential. A cDNA was cloned that, when expressed in yeast, was shown to result in desaturation of 18:3n−3 and 18:2n−6, indicating that it coded for a Δ6 desaturase enzyme. Very low desaturation of 20:4n−3 and 20:3n−6 indicated only trace Δ5 activity. Another cloned cDNA enabled elongation of 18:4n−3, 18:3n−6, 20:5n−3 and 20:4n−6 in the yeast expression system, indicating that it had C18–20 and C20–22 elongase activity. Sequence comparison and phylogenetic analysis confirmed that it was homologous to human ELOVL5 elongase. However, the cobia Elovl5 elongase also had low activity toward C24 HUFA. The cobia Δ6 desaturase had a preference for 18:3n−3, but the elongase was generally equally active with both n−3 and n−6 substrates. Expression of both genes was 1–2 orders of magnitude greater in brain than other tissues suggesting an important role, possibly to ensure sufficient docosahexaenoic acid (DHA, 22:6n−3) synthesis in neural tissues through elongation and desaturation of eicosapentaenoic acid (EPA; 20:5n−3).

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By Team FPS – February 21, 2012

Estrogen and PCOS

Also see:
Thyroid disorders in polycystic ovarian syndrome subjects: A tertiary hospital based cross-sectional study from Eastern India
Childhood conditions influence adult progesterone levels
W.D. Denckla, A.V. Everitt, Hypophysectomy, & Aging
Removal of the Pituitary: Slows Aging and Hardening of Collagen

Quotes by Ray Peat, PhD:
“Besides providing new insights into biological energy and aging, the recognition that estrogen activates the stress hormone system–the pituitary-adrenal system–also provides clear insights into other problems, such as the polycystic ovary syndrome, hirsutism, adrenal hyperplasia, Cushing’s disease, etc.”

“If your thyroid is working efficiently, your pituitary doesn’t have much to do and you’re not likely to get a pituitary tumor, your adrenals don’t have much to do, and your ovaries don’t get over stimulated. The other glands have an easy job when your thyroid is working right. If your thyroid gets interfered with, you have to rev up your adrenals and your pituitary becomes commander in chief and tells everyone what to do.”

“PCOS can be produced in animals by removing the thyroid gland. The inability of ovaries to make progesterone without thyroid causes the adrenals to be overstimulated, and they are the source of increased DHEA and other androgens and estrogen.”

“Many factors, including poor nutrition, climate, emotional or physical stress (even excessive running) and toxins, can cause a progesterone deficiency. Use of estrogens, birth control pills and even IUDs can also bring about a deficiency. Animal studies and clinical experience suggests that the prenatal hormonal environment (a mother’s excess of estrogen during pregnancy) can incline a person toward a deficiency of progesterone relative to estrogen.”

“Estrogen, at least when it is not opposed by a very large concentration of progesterone, creates all of the conditions known to be involved in the aging process. These effects of estrogen include interference with oxidative metabolism, formation of lipofuscin (the age-pigment), retention of iron, production of free radicals and lipid peroxides, promotion of excitotoxicity and death of nerve cells, impaired learning ability, increased tendency to form blood clots and to have vascular spasms, increased autoimmunity and atrophy of the thymus, elevated prolactin, atrophy of skin, increased susceptibility to a great variety of cancers, lowered body temperature, lower serum albumin, increased tendency toward edema, and many of the features of shock. In recent years, it has been found to be responsible even for neonatal masculinization and the masculinization of the polycystic ovary syndrome. Although the pharmaceutical industry has often referred to it as “the female hormone,” I don’t know of any competent scientist who has ever called it that.”

Am J Obstet Gynecol. 1993 Nov;169(5):1223-6.
Excessive estradiol secretion in polycystic ovarian disease.
Benjamin F, Toles AW, Seltzer VL, Deutsch S.
Polycystic ovarian disease is both a hyperestrogenic and a hyperandrogenic syndrome, and all studies have shown that hyperestrogenemia is the result of an elevation of estrone with plasma estradiol levels in the normal follicular range. Because a literature search failed to reveal any report of polycystic ovarian disease with significantly elevated estradiol levels, we report a case in which the plasma estradiol was so massively elevated as to mimic an estrogen-producing neoplasm. This case also suggests that although polycystic ovarian disease is a very rare cause of such excessive estradiol production, it should be included in the differential diagnosis of estrogen-producing neoplasms.

J Clin Endocrinol Metab. 1995 Feb;80(2):603-7.
The impact of estrogen on adrenal androgen sensitivity and secretion in polycystic ovary syndrome.
Ditkoff EC, Fruzzetti F, Chang L, Stancyzk FZ, Lobo RA.
Adrenal hyperandrogenism is a common feature of patients with polycystic ovary syndrome (PCO). This may be due to enhanced adrenal sensitivity to ACTH. Because enhanced ovarian androgen secretion does not appear to explain this phenomenon, we explored the role of estrogen in inducing enhanced adrenal sensitivity, in that a state of relative hyperestrogenism exists in PCO. Eight patients with PCO and seven matched controls received ovine corticotropin-releasing hormone (oCRH; 0.1 micrograms/kg) iv before and after hypoestrogenism was induced by leuprolide acetate (LA; 1 mg, sc, each day). In patients with PCO, a third oCRH test was repeated after transdermal estradiol (E2; 0.1 mg) had been applied for a week, during which time LA was continued. At baseline, patients with PCO had increased responses of 11 beta-hydroxyandrostenedione and dehydroepiandrosterone (P < 0.03 and P < 0.02) and increased delta maximal ratios of androstenedione (A4)/ACTH and dehydroepiandrosterone/ACTH (P < 0.01) after oCRH treatment. After LA administration to patients with PCO, these ratios were significantly suppressed (P < 0.01) and returned to baseline after E2 was added. There were no changes in controls. Steroid ratio responses to oCRH suggested that 17,20-desmolase activity (delta maximum change in the ratio of A4/17-hydroxyprogesterone) was lowered with estrogen suppression and increased again after transdermal E2 administration. There was a significant positive correlation between changes in E2 levels and delta maximum change in the ratios of A4/17-OHP after oCRH treatment, signifying 17,20-desmolase activity (r = 0.58, P < 0.02). In conclusion, these data provide evidence that estrogen is at least one factor that influences adrenal androgen sensitivity in PCO and may help explain the frequent finding of adrenal hyperandrogenism in this syndrome.

Endocrinology. 1993 Dec;133(6):2696-703.
Ovarian steroidal response to gonadotropins and beta-adrenergic stimulation is enhanced in polycystic ovary syndrome: role of sympathetic innervation.
Barria A, Leyton V, Ojeda SR, Lara HE.
Experimental induction of a polycystic ovarian syndrome (PCOS) in rodents by the administration of a single dose of estradiol valerate (EV) results in activation of the peripheral sympathetic neurons that innervate the ovary. This activation is evidenced by an increased capacity of ovarian nerve terminals to incorporate and release norepinephrine (NE), an increase in ovarian NE content, and a decrease in ovarian beta-adrenergic receptor number in the ovarian compartments receiving catecholaminergic innervation. The present experiments were undertaken to examine the functional consequences of this enhanced sympathetic outflow to the ovary. The steroidal responses of the gland to beta-adrenergic receptor stimulation and hCG were examined in vitro 60 days after EV administration, i.e. at the time when follicular cysts are well established. EV-treated rats exhibited a remarkable increase in ovarian progesterone and androgen responses to isoproterenol, a beta-adrenergic receptor agonist, with no changes in estradiol responsiveness. Basal estradiol release was, however, 50-fold higher than the highest levels released from normal ovaries at any phase of the estrous cycle. The ovarian progesterone and androgen responses to hCG were enhanced in EV-treated rats, as were the responses to a combination of isoproterenol and hCG. Transection of the superior ovarian nerve (SON), which carries most of the catecholaminergic fibers innervating endocrine ovarian cells, dramatically reduced the exaggerated responses of all three steroids to both beta-adrenergic and gonadotropin stimulation. SON transection also reduced the elevated levels of ovarian NE resulting from EV treatment and caused up-regulation of beta-adrenoreceptors. Most importantly, SON transection restored estrous cyclicity and ovulatory capacity. The results indicate that the increased output of ovarian steroids in PCOS is at least in part due to an enhanced responsiveness of the gland to both catecholaminergic and gonadotropin stimulation. The ability of SON transection to restore a normal response indicates that the alteration in steroid output results from a deranged activation of selective components of the noradrenergic innervation to the ovary. These findings support the concept that an alteration in the neurogenic control of the ovary contributes to the etiology of PCOS.

Br J Obstet Gynaecol. 1976 Aug;83(8):593-602.
Polycystic ovarian disease.
Duignan NM.
Sex hormone binding globulin (SHBG) capacity was reduced in 9 of 31 patients with polycystic ovarian (PCO) disease and the mean level in PCO patients was significantly less (p less than 0.001) than normal. Serum testosterone levels were elevated in 21 of 32 PCO patients and the mean level was significantly elevated (p less than 0.001). Serum androstenedione values were raised in 17 of 31 patients and the mean value was also significantly raised (p less than 0.001). Serum dehydroepiandrosterone sulphate (DHAS) concentrations were elevated in only 2 of 14 patients. Urinary 17-oxo and 17-oxogenic steroids were normal in all patients studied. Basal follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were normal but LH release following injection of luteinizing hormone-releasing hormone (LH-RH) was enhanced. A highly significant negative correlation (r=–0.449; p less than 0.01) was found between the logarithm of testosterone and the logarithm of LH levels. Serum prolactin concentrations were elevated in 4 of 21 PCO patients. Thyroid-stimulating hormone (TSH) values were normal. Eighteen of 20 patients ovulated following treatment with clomiphene and nine became pregnant. Five of 12 of patients treated with oestrogen/progesterone preparations noticed an improvement in their hirsutism. It is suggested that the normal cyclical release of LH is inhibited in PCO disease by a negative feedback by androgens to the hypothalamus or the pituitary, and that wedge resection should be reserved for patients in whom other forms of treatment have failed.

Akush Ginekol (Mosk). 1990 Sep;(9):61-3.
[The therapeutic effect of parlodel in the polycystic ovary syndrome].
[Article in Russian]
Soboleva EL, Komarov EK, Potin VV, Svechnikova FA.
Parlodel (2.5-50 mg/day) has been given for 1 to 7 days to 33 patients with the polycystic ovary syndrome (POS). The ovulatory menstrual cycle returned in 10 (30%) patients and 4 of them conceived. Pretreatment cycle disturbance persisted in 6 (18%) patients. Parlodel reduced mid-follicular mean blood LH levels to values of normal women. Some decrease in blood testosterone levels occurred only in the second phase of the cycle. Estradiol test in 6 patients showed normal positive and negative feedbacks in the hypothalamic-pituitary-ovarian axis. Parlodel treatment reduced basal and estradiol stimulated pituitary gonadotropin secretion. It is suggested that parlodel may be used in ovulation induction in a proportion of POS patients.

Obstet Gynecol. 1980 May;55(5):579-82.
Prolactin release in polycystic ovary.
Falaschi P, del Pozo E, Rocco A, Toscano V, Petrangeli E, Pompei P, Frajese G.
Ten normoprolactinemic and 10 hyperprolactinemic patients, all with polycystic ovary syndrome (PCO), were subjected to prolactin (PRL) stimulatory tests with thyrotropin-releasing hormone (TRH), 200 microgram intravenously, and haloperidol (a dopamine-blocking agent), 1 mg intramuscularly. The results were compared with those of 8 women with idiopathic hyperprolactinemia and 10 normal female volunteers. Distinctive features of PCO were elevated plasma concentrations of luteinizing hormone, estrone, and testosterone in the presence of normal estradiol, whereas in idiopathic hyperprolactinemia estradiol was reduced. Both groups of patients with PCO exhibited responses to TRH and haloperidol significantly higher than the controls (P less than .001), whereas only the hyperprolactinemic PCO patients reacted with an excessive PRL discharge (P less than .001). As expected, the response to both secretagogue agents was blunted in patients with idiopathic hyperprolactinemia. The present report discusses the possible implication of estrogen and the dopaminergic system in the mechanisms leading to hyperprolactinemia and enhanced PRL release in PCO.

The Journal of Clinical Endocrinology & Metabolism September 1, 1996 vol. 81 no. 9 3299-3306
The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome.
A Dunaif, D Scott, D Finegood, B Quintana and R Whitcomb
We performed this study to investigate the hypothesis that insulin resistance plays a role in the pathogenesis of reproductive abnormalities in women with the polycystic ovary syndrome (PCOS). Twenty-five women with PCOS were enrolled in a double-blind randomized 3-month trial of two doses of the insulin-sensitizing agent, troglitazone, 21 of whom completed the study: 200 mg, n = 10; 400 mg, n = 11. Baseline hormonal parameters and glucose tolerance were compared with 12 age- and weight-matched ovulatory control women. There were no significant changes in body mass index during the study. Fasting (P < 0.01) and 2-h post-75-g glucose load insulin levels (P < 0.05), as well as integrated insulin responses to the glucose load, decreased (P < 0.05), and insulin sensitivity assessed by a frequently sampled iv glucose tolerance test increased significantly (P < 0.001) during troglitazone treatment. This was accompanied by significant decreases in the levels of nonsex hormone-binding globulin-bound testosterone (P < 0.01), dehydroepiandrosterone sulfate (P < 0.001), estradiol (P < 0.01), and estrone (P < 0.001). Stepwise regression analysis indicated that decreases in nonsex hormone-binding globulin testosterone levels were significantly correlated with decreases in integrated insulin responses to the glucose load (r2 0.44, P < 0.01). The only significant changes at the 200-mg troglitazone dose were an increase in insulin sensitivity (P < 0.05) and decreases in dehydro-epiandrosterone sulfate (P < 0.01) and estrone (P < 0.05) levels. At the 400-mg dose, in addition to the changes noted in the entire troglitazone treatment group, increases in the disposition index (the product of insulin sensitivity and secretion) achieved significance, as did decreases in androstenedione (P < 0.01) and LH (P < 0.05) levels and increases in sex hormone-binding globulin levels (P < 0.01). Two PCOS women had ovulatory menses. We conclude that 1) troglitazone improves total body insulin action in PCOS, resulting in lower circulating insulin levels; 2) insulin resistance, probably via hyperinsulinemia, results in a general augmentation of steroidogenesis and LH release in PCOS; and 3) insulin-sensitizing agents, such as troglitazone, may provide a novel therapy for PCOS.

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By Team FPS – February 17, 2012

Shock Increases Estrogen

Also see:
Resuscitation: Benefits of ATP, Glucose, and Sodium
Trauma & Resuscitation: Toxicity of Lactated Ringer’s Solution
Autoimmune Disease and Estrogen Connection
Hormonal profiles in women with breast cancer
PUFA Increases Estrogen
PUFA Inhibit Glucuronidation
PUFA Promote Cancer
Maternal PUFA Intake Increases Breast Cancer Risk in Female Offspring
Vitamin A: Anti-Cancer and Anti-Estrogen
Toxic Plant Estrogens
The Dire Effects of Estrogen Pollution
Progesterone: Essential to Your Well-Being
Alcohol Consumption – Estrogen and Progesterone In Women
Estrogen, Endotoxin, and Alcohol-Induced Liver Injury
Estrogen Levels Increase with Age
Fat Tissue and Aging – Increased Estrogen
Estrogen Related to Loss of Fat Free Mass with Aging
Bisphenol A (BPA), Estrogen, and Diabetes

“Since Selye’s work, it has been known that estrogen creates the same conditions as occur in the shock phase of the stress reaction. (And shock, in a potential vicious circle, can increase the level of estrogen.)” -Ray Peat, PhD

Circ Shock. 1994 Aug;43(4):171-8.
Sex steroid hormones in circulatory shock, sepsis syndrome, and septic shock.
Fourrier F, Jallot A, Leclerc L, Jourdain M, Racadot A, Chagnon JL, Rime A, Chopin C.
METHODS:
Estrone (E1), estradiol (E2), testosterone (T), FSH, and LH levels were daily measured during a ten day period in 50 critically ill patients (38 men, 12 post-menopausal women). Patients were separated into four groups: A) no circulatory failure, no sepsis, B) sepsis syndrome without circulatory failure, C) circulatory failure without sepsis syndrome, D) septic shock. Results of hormonal measurements were compared 1) among the 4 groups, 2) between male and female patients, 3) between septic and nonseptic patients. The potential for the infusion of the vasoactive drug dobutamine to induce sex hormonal changes was documented in ten additional septic shock patients by measuring cortisol, E1, and T at base-line and after dobutamine infusion. Changes in active renin and plasma renin activity (PRA) were used as indirect witness of the dobutamine-induced beta 2-stimulation.
RESULTS:
A dramatic increase in E1 and E2 levels was observed in women of groups B and D, and only in male patients of group D. In the septic patients, estrogen levels peaked at days 1 and 2 and trended to normal from day 6 after the onset of sepsis, while FSH and LH decreased. No difference was found between survivors and non-survivors. Whatever the group, male patients had low T levels throughout the study. Dobutamine induced a significant increase in active renin levels and a decrease in the regression slope between renin and PRA. Cortisol levels remained normal. No significant change in E1 and T was observed after dobutamine.
CONCLUSIONS:
High estrogen levels were specifically observed in patients with sepsis and septic shock, either males or females. Decreased LH and FSH levels were consistent with the negative feed-back effect of high estrogen levels on pituitary secretion. Circulating T levels were decreased in all male patients. We found no correlation between sequential estrogen levels and outcome. These levels were not modified by a dobutamine-induced beta-2 stimulation.

==========================================
Progesterone protects against shock:

Crit Care Med. 2003 Jun;31(6):1786-93.
Progesterone administration after trauma and hemorrhagic shock improves cardiovascular responses.
Kuebler JF1, Jarrar D, Bland KI, Rue L 3rd, Wang P, Chaudry IH.
OBJECTIVE:
Studies have shown that female rats during the proestrus stage have significantly improved cell and organ functions after trauma-hemorrhage compared with male and ovariectomized females. This study investigated the hypothesis that progesterone can improve the depressed cardiovascular function in sex steroid-deficient female rats (i.e., ovariectomized females) after trauma-hemorrhage and resuscitation.
DESIGN:
Prospective study.
SETTING:
University laboratory.
SUBJECTS:
Ovariectomized female Sprague-Dawley rats (weight, 250-300 g).
INTERVENTIONS:
Rats underwent a 5-cm midline laparotomy (i.e., soft-tissue trauma), were bled to a mean arterial pressure of 35 mm Hg for approximately 90 mins, and were then resuscitated using Ringer’s lactate. A single dose of progesterone (25 mg/kg of body weight) or vehicle was administered subcutaneously during resuscitation.
MEASUREMENTS:
At 20 hrs after trauma-hemorrhage or sham operation, cardiac output and heart performance and the circulating blood volume were assessed using the indocyanine green dilution technique and a left ventricular catheter. Furthermore, the binding activity of progesterone receptors in nuclear extracts of left ventricular tissue was determined.
RESULTS:
Cardiac output, heart performance, and circulating blood volume were significantly decreased in vehicle-treated animals after trauma-hemorrhage. Administration of progesterone significantly improved cardiac output and heart performance and increased the circulating blood volume. This was associated with an increased progesterone receptor activity in the left ventricular nuclear extracts.
CONCLUSION:
Because administration of progesterone after trauma-hemorrhage in sex steroid-deficient females improved cardiovascular responses, this hormone seems to be a useful adjunct for the treatment of cardiovascular depression in postmenopausal and ovariectomized female trauma patients.

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By Team FPS – February 17, 2012

Bisphenol A (BPA), Estrogen, and Development

The estrogenic effects of bisphenol A (BPA) create a potential model of estrogen’s harm of mother and fetus.

Arch Toxicol. 2006 Oct;80(10):647-55. Epub 2006 Apr 8.
Toxicokinetics of bisphenol A in pregnant DA/Han rats after single i.v. application.
Moors S, Diel P, Degen GH.
Bisphenol A (BPA) is an important chemical in the production of epoxy resins and polycarbonate plastics, and basic monomers which are used for a variety of applications. Consumer exposure to BPA may be possible from migration of BPA from dental sealants or from polycarbonate or epoxy-lined food and drink containers. BPA is known to act as weak estrogen mimic in rodents, and there is a concern of adverse endocrine effects, especially from prenatal exposure to this potential ‘endocrine disruptor’. To address this concern, we have studied the disposition and transplacental transfer of BPA in pregnant DA/Han rats on day 18 of gestation. The BPA concentrations were determined by GC/MS analysis in maternal blood, maternal organs (liver, kidney, uterus), placenta and fetuses (fetal liver and residual tissues) at different time-points (5-360 min) after intravenous administration of 10 mg BPA/kg body weight. Total BPA (aglycone and conjugates) was analyzed in all tissue samples after enzymatic hydrolysis and liquid/liquid extraction; in maternal plasma, total BPA and BPA aglycone were analyzed in parallel samples (with/without hydrolysis). Soon (5 min) after the i.v. injection a mean total BPA concentration of 3.8 microg/ml was found in maternal plasma; it declined in the first 2 h to 0.7 microg/ml. Early after injection, the majority of circulating BPA (almost 80%) was still in the aglycone form, but, metabolism by phase II enzymes decreased the BPA aglycone concentration to 0.3 microg/ml after 2 h. Despite this efficient conjugation, BPA was rapidly distributed in the organism: In well perfused organs peak concentrations for total BPA were attained 20-30 min after intravenous administration, with mean values of about 9.7 microg/g in maternal liver, 8.6 microg/g in kidneys, and 6.2 microg/g in the uterus. The peak values in other tissues were lower, with 4.0 microg/g for placenta, 3.3 microg/g for fetal liver, and 2.4 microg/g for residual fetus homogenate. The BPA levels in all tissues thereafter declined more or less in parallel with those in maternal blood. The rather similar concentration time course in placenta and fetal liver indicates that BPA is readily transferred across the placenta of DA/Han rats to the fetus. Our data on BPA disposition in DA/Han rats are discussed in the context of other kinetic studies with BPA in pregnant rats, and in relation to the previous results from our laboratory (Degen et al. Arch Toxicol 76:23-29, 2002a, b, c) demonstrating comparable transplacental transfer of daidzein, a phytoestrogen that accounts for a significant portion of total human exposure to potential endocrine disruptors.

Neuroscience. 2010 May 19;167(3):741-9. Epub 2010 Feb 26.
Corticosterone-regulated actions in the rat brain are affected by perinatal exposure to low dose of bisphenol A.
Poimenova A, Markaki E, Rahiotis C, Kitraki E.
The estrogen-mimicking endocrine disrupter bisphenol A (BPA) which is used in the manufacture of plastic and epoxy resins, is one of the world’s most heavily produced synthetic chemicals. BPA is detected in animal tissues, and its bio-accumulation has shown to be higher in the fetus than the mother. Exposure to doses below the daily safe limit has been reported to affect the sexual differentiation of the brain and modify the behavior of the exposed rodent offspring. The aim of the present study was to investigate in the rat the possible organizational effects of low BPA exposure on glucocorticoid-regulated responses. Female breeders were exposed to 40 microg/kg b.w. BPA daily throughout pregnancy and lactation. Plasma corticosterone levels and the two types of hippocampal corticosteroid receptors (GR and MR) were determined in mid-adolescent offspring under basal conditions and following a Y-maze task. BPA treated females had higher corticosterone levels than control females and BPA males and lower GR levels than BPA males, under basal conditions. Following the mildly stressful experience of Y-maze, corticosterone levels were increased in BPA-treated animals of both sexes, compared to the controls. GR levels were also increased in BPA-treated females compared to males. No effect of BPA was observed on MR levels, whereas the Y-maze experience significantly decreased receptors’ levels in both female groups. The animals’ performance in the task was also evaluated. BPA exposure significantly impaired the spatial recognition memory in both sexes, and modified the behavioural coping in a sex-dependent manner. Female BPA-treated offspring exhibited increased “anxiety-like” behaviour and dramatic loss of exploration attitude during the task, in comparison to males. This study provides for the first time evidence that corticosterone and its actions in the brain are sensitive to the programming effects of BPA at a dose below the currently acceptable daily intake.

Synapse. 2010 Jun;64(6):432-9.
Prenatal and postnatal exposure to bisphenol a induces anxiolytic behaviors and cognitive deficits in mice.
Tian YH, Baek JH, Lee SY, Jang CG.
Bisphenol A (BPA), an environmental endocrine-disrupting chemical, has been extensively evaluated for reproductive toxicity and carcinogenicity. However, little is known about the behavioral and neurochemical effects of BPA exposure. This study examined whether chronic daily exposure to an environmental endocrine-disrupting chemical, bisphenol A [(BPA); 100 microg/kg/day or 500 microg/kg/day, p.o.], from prenatal Day 7 to postnatal Day 36 would lead to changes in anxiety and memory in mice. First, we observed the behavioral alterations of BPA-treated mice using two anxiety-related models, the open field test and elevated plus maze (EPM) test. In the open field test, BPA treatment (100 microg/kg/day) increased movement in the central zone. BPA treatment (500 microg/kg/day) also increased the time spent in the open arms in the EPM test. Second, we measured cognitive ability in the Y-maze test and novel object test. BPA-treated mice showed decreased alternation behavior in the Y-maze at both of doses, indicating working memory impairment. BPA-treated mice (100 microg/kg/day) also showed decreased novel object recognition as expressed by central locomotion and frequency in the central zone, showing recognition memory impairment. Finally, to measure changes in the dopaminergic and NMDAergic systems in the brain, we performed autoradiographic receptor binding assays for dopamine D(1) and D(2) receptors, the NMDA receptor, and the dopamine transporter. BPA treatment increased D(2) receptor binding in the caudate putamen (CPu) but decreased DAT binding. BPA treatment also decreased NMDA receptor binding in the frontal cortex and CA1, CA3, and DG of the hippocampus. Taken together, our results suggest that long-term BPA exposure in mice can induce anxiolytic behaviors, cognitive deficits and changes in the dopaminergic and NMDAergic systems.

Horm Behav. 2010 Jul;58(2):326-33. Epub 2010 Mar 3.
Perinatal exposure to bisphenol-A impairs learning-memory by concomitant down-regulation of N-methyl-D-aspartate receptors of hippocampus in male offspring mice.
Xu XH, Zhang J, Wang YM, Ye YP, Luo QQ.
Bisphenol-A (BPA) has been shown to influence development of the brain and behaviors. The purpose of the present report was to investigate the effects of perinatal exposure to BPA on learning/memory and its mechanism of action, especially focusing on N-methyl-d-aspartate receptor (NMDAR). Perinatal maternal exposure to BPA at 0.5, 5, and 50mg/kg/d significantly extended the escape length to find the hidden platform in Morris water maze, and BPA at 0.5 or 5mg/kg/d markedly decreased the percentage of time spent in the quadrant where the platform had been during training both in postnatal day (PND) 21 and PND 56 mice. The results of passive avoidance test showed that the error frequency to step down from a platform after received footshock was significantly increased, and the latency of the step-down response onto the grid floor 24h after received footshock was obviously reduced by exposure to BPA at 5 and 50mg/kg/d (P<0.01) in the PND 21 offspring or at 50mg/kg/d in the PND 56 offspring (P<0.01). Furthermore, perinatal exposure to BPA significantly inhibited the expressions of NMDAR subunits NR1, NR2A, and 2B in the hippocampus during the development stage, especially in PND 56 mice. The expressions of estrogen receptor beta (ERbeta) in both PND 21 and PND 56 mice were markedly down-regulated by BPA at 0.5, 5, and 50mg/kg/d. These results indicate that perinatal exposure to BPA affects normal behavioral development in both spatial memory and avoidance memory, and also permanently influences the behavior of offspring in adulthood. The inhibition of expressions of NMDAR subunits and ERbeta in hippocampus during postnatal development stage may be involved.

Environ Health Perspect. 2001 Jul;109(7):675-80.
Perinatal exposure to low doses of bisphenol A affects body weight, patterns of estrous cyclicity, and plasma LH levels.
Rubin BS, Murray MK, Damassa DA, King JC, Soto AM.
The nonsteroidal estrogenic compound bisphenol A (BPA) is a monomer used in the manufacture of polycarbonate plastics and resins. BPA may be ingested by humans as it reportedly leaches from the lining of tin cans into foods, from dental sealants into saliva, and from polycarbonate bottles into their contents. Because BPA is weakly estrogenic–approximately 10,000-fold less potent than 17beta-estradiol–current environmental exposure levels have been considered orders of magnitude below the dose required for adverse effects on health. Herein we demonstrate measurable effects on the offspring of Sprague-Dawley female rats that were exposed, via their drinking water, to approximately 0.1 mg BPA/kg body weight (bw)/day (low dose) or 1.2 mg BPA/kg bw/day (high dose) from day 6 of pregnancy through the period of lactation. Offspring exposed to BPA exhibited an increase in body weight that was apparent soon after birth and continued into adulthood. In addition, female offspring exposed perinatally to the high dose of BPA exhibited altered patterns of estrous cyclicity and decreased levels of plasma luteinizing hormone (LH) in adulthood. Administration of neither the doses of BPA that caused effects during perinatal exposure nor a 10-fold higher dose was able to evoke a uterotropic response in ovariectomized postpubertal females. These data indicate an increased sensitivity to BPA during the perinatal period and suggest the need for careful evaluation of the current levels of exposure to this compound.

Environ Res. 2008 Oct;108(2):150-7.
Effects of developmental exposure to bisphenol A on brain and behavior in mice.
Palanza P, Gioiosa L, vom Saal FS, Parmigiani S.
Bisphenol A (BPA) is a widespread estrogenic chemical used in the production of polycarbonate, and epoxy resins lining food and beverage cans and in dental sealants. During fetal life the intrauterine environment is critical for the normal development, and even small changes in the levels of hormones, such as estradiol or estrogen-mimicking chemicals, can lead to changes in brain function and consequently in behavior. We review here a series of ethological studies on the effects of maternal oral exposure during the last part of gestation (prenatal exposure) or from gestation day 11 to postnatal day 7 (perinatal exposure) to a low, environmentally relevant dose of BPA (10 microg/kg bw/day) on behavioral responses of CD-1 mouse offspring. We examined both male and female offspring and found that maternal exposure to BPA affected: (1) behavioral responses to novelty before puberty and, as adults; (2) exploration and activity in a free-exploratory open field; (3) exploration in the elevated plus maze and (4) sensitivity to amphetamine-induced reward in the conditioned place preference test. A consistent effect of the maternal exposure to BPA is that in all these different experimental settings, while a significant sex difference was observed in the control group, exposure to BPA decreased or eliminated the sex difference in behavior. In addition, exposure of female mice to BPA in both adulthood or during fetal life altered subsequent maternal behavior. These findings, together with those from other laboratories, are evidence of long-term consequences of maternal exposure to low-dose BPA at the level of neurobehavioral development.

Horm Behav. 2007 Sep;52(3):307-16. Epub 2007 May 22.
Developmental exposure to low-dose estrogenic endocrine disruptors alters sex differences in exploration and emotional responses in mice.
Gioiosa L, Fissore E, Ghirardelli G, Parmigiani S, Palanza P.
Estrogenic endocrine disruptors (EEDs) are naturally occurring or man-made compounds present in the environment that are able to bind to estrogen receptors and interfere with normal cellular development in target organs and tissues. There is mounting evidence that EEDs can interfere with the processes of sexual differentiation of brain and behavior in different animal models. We investigated the effects of maternal exposure to EEDs, at concentrations within the range of human exposure and not patently teratogenic, on behavioral responses of male and female house mice (Mus musculus domesticus) before and after puberty. Pregnant dams were trained to spontaneously drink daily doses of corn oil with or without the estrogenic plastic derivative, bisphenol A (BPA 10 microg/kg), or the estrogenic insecticide methoxychlor (MXC 20 microg/kg) from gestation day 11 to postpartum day 8. Their male and female offspring were examined at different ages to examine several components of explorative and emotional behaviors in 3 experimental paradigms: a novelty test before puberty and, as adults, a free-exploratory open-field test and the elevated plus maze test. The main results are sex differences in control mice on a number of behavioral responses at both ages and in all experimental paradigms, while perinatal exposure to BPA or MXC decreased or eliminated such sex differences. The present findings are evidence of long-term consequences of developmental exposure to BPA and MXC on neurobehavioral development and suggest a differential effect of low-dose exposure to these estrogenic chemicals in males and females.

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By Team FPS – February 17, 2012

Bisphenol A (BPA), Estrogen, and Diabetes

Also see:
Estrogen and Glucose Intolerance
Estrogen Stimulates Insulin, Lowers Blood Sugar, Depletes Glycogen
The Randle Cycle
Diabetes: Conversion of Alpha-cells into Beta-cells

Mol Cell Endocrinol. 2011 Dec 31. [Epub ahead of print]
Bisphenol-A acts as a potent estrogen via non-classical estrogen triggered pathways.
Alonso-Magdalena P, Ropero AB, Soriano S, García-Arévalo M, Ripoll C, Fuentes E, Quesada I, Nadal A.
Bisphenol-A (BPA) is an estrogenic monomer commonly used in the manufacture of numerous consumer products such as food and beverage containers. Widespread human exposure to significant doses of this compound has been reported. Traditionally, BPA has been considered a weak estrogen, based on its lower binding affinity to the nuclear estrogen receptors (ERs) compared to 17-β estradiol (E2) as well as its low transcriptional activity after ERs activation. However, in vivo animal studies have demonstrated that it can interfere with endocrine signaling pathways at low doses during fetal, neonatal or perinatal periods as well as in adulthood. In addition, mounting evidence suggests a variety of pathways through which BPA can elicit cellular responses at very low concentrations with the same or even higher efficiency than E2. Thus, the purpose of the present review is to analyze with substantiated scientific evidence the strong estrogenic activity of BPA when it acts through alternative mechanisms of action at least in certain cell types.

Endocrinology. 2006 Jun;147(6 Suppl):S56-69. Epub 2006 May 11.
Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure.
Welshons WV, Nagel SC, vom Saal FS.
Over 6 billion pounds per year of the estrogenic monomer bisphenol A (BPA) are used to manufacture polycarbonate plastic products, in resins lining metal cans, in dental sealants, and in blends with other types of plastic products. The ester bond linking BPA molecules in polycarbonate and resins undergoes hydrolysis, resulting in the release of free BPA into food, beverages, and the environment, and numerous monitoring studies now show almost ubiquitous human exposure to biologically active levels of this chemical. BPA exerts estrogenic effects through the classical nuclear estrogen receptors, and BPA acts as a selective estrogen receptor modulator. However, BPA also initiates rapid responses via estrogen receptors presumably associated with the plasma membrane. Similar to estradiol, BPA causes changes in some cell functions at concentrations between 1 pM and 1 nM, and the mean and median range of unconjugated BPA measured by multiple techniques in human pregnant maternal, fetal, and adult blood and other tissues exceeds these levels. In contrast to these published findings, BPA manufacturers persist in describing BPA as a weak estrogen and insist there is little concern with human exposure levels. Our concern with human exposure to BPA derives from 1) identification of molecular mechanisms mediating effects in human and animal tissues at very low doses, 2) in vivo effects in experimental animals caused by low doses within the range of human exposure, and 3) widespread human exposure to levels of BPA that cause adverse effects in animals.

Reprod Toxicol. 2007 Aug-Sep;24(2):199-224. Epub 2007 Jun 26.
In vivo effects of bisphenol A in laboratory rodent studies.
Richter CA, Birnbaum LS, Farabollini F, Newbold RR, Rubin BS, Talsness CE, Vandenbergh JG, Walser-Kuntz DR, vom Saal FS.
Concern is mounting regarding the human health and environmental effects of bisphenol A (BPA), a high-production-volume chemical used in synthesis of plastics. We have reviewed the growing literature on effects of low doses of BPA, below 50 mg/(kg day), in laboratory exposures with mammalian model organisms. Many, but not all, effects of BPA are similar to effects seen in response to the model estrogens diethylstilbestrol and ethinylestradiol. For most effects, the potency of BPA is approximately 10-1000-fold less than that of diethylstilbestrol or ethinylestradiol. Based on our review of the literature, a consensus was reached regarding our level of confidence that particular outcomes occur in response to low dose BPA exposure. We are confident that adult exposure to BPA affects the male reproductive tract, and that long lasting, organizational effects in response to developmental exposure to BPA occur in the brain, the male reproductive system, and metabolic processes. We consider it likely, but requiring further confirmation, that adult exposure to BPA affects the brain, the female reproductive system, and the immune system, and that developmental effects occur in the female reproductive system.

Environ Health Perspect. 2006 Jan;114(1):106-12.
The estrogenic effect of bisphenol A disrupts pancreatic beta-cell function in vivo and induces insulin resistance.
Alonso-Magdalena P, Morimoto S, Ripoll C, Fuentes E, Nadal A.
The function of the pancreatic beta-cell is the storage and release of insulin, the main hormone involved in blood glucose homeostasis. The results in this article show that the widespread environmental contaminant bisphenol-A (BPA) imitates 17beta-estradiol (E2) effects in vivo on blood glucose homeostasis through genomic and nongenomic pathways. The exposure of adult mice to a single low dose (10 microg/kg) of either E2 or BPA induces a rapid decrease in glycemia that correlates with a rise of plasma insulin. Longer exposures to E2 and BPA induce an increase in pancreatic beta-cell insulin content in an estrogen-receptor-dependent manner. This effect is visible after 2 days of treatment and starting at doses as low as 10 microg/kg/day. After 4 days of treatment with either E2 or BPA, these mice developed chronic hyperinsulinemia, and their glucose and insulin tolerance tests were altered. These experiments unveil the link between environmental estrogens and insulin resistance. Therefore, either abnormal levels of endogenous estrogens or environmental estrogen exposure enhances the risk of developing type 2 diabetes mellitus, hypertension, and dyslipidemia.

Int J Androl. 2008 Apr;31(2):194-200. Epub 2007 Oct 31.
Bisphenol-A disruption of the endocrine pancreas and blood glucose homeostasis.
Ropero AB, Alonso-Magdalena P, García-García E, Ripoll C, Fuentes E, Nadal A.
The link between endocrine disruptors and altered blood glucose homeostasis has been recently suggested. Epidemiological studies have correlated levels of phthalates, dioxins and persistent organic pollutants with alterations of blood glucose homeostasis in humans. Environmentally relevant doses of the ubiquitous endocrine disruptor bisphenol-A (BPA) have profound effects on mice endocrine pancreas–an essential tissue involved in glucose metabolism. BPA exerts rapid non-genomic effects on insulin releasing beta-cells and glucagon releasing alpha-cells within freshly isolated islets of Langerhans. In vivo, a single BPA injection of 10 microg/kg rapidly increases plasma insulin and concomitantly decreases glycaemia. When mice were treated with BPA 100 microg/kg/day for 4 days, the environmental oestrogen produced an increase in beta-cell insulin content along with a post-prandial hyperinsulinaemia and insulin resistance. The results reviewed here demonstrate that doses well below the current lowest observed adverse effect level considered by the US-EPA, disrupt pancreatic beta-cell function producing insulin resistance in male mice. Therefore, this altered blood glucose homeostasis by BPA exposure may enhance the risk of developing type II diabetes.

Mol Cell Endocrinol. 2009 May 25;304(1-2):63-8. Epub 2009 Mar 9.
The pancreatic beta-cell as a target of estrogens and xenoestrogens: Implications for blood glucose homeostasis and diabetes.
Nadal A, Alonso-Magdalena P, Soriano S, Quesada I, Ropero AB.
The estrogen receptor ERalpha is emerging as a key molecule involved in glucose and lipid metabolism. The main functions of pancreatic beta-cells are the biosynthesis and release of insulin, the only hormone that can directly decrease blood glucose levels. Estrogen receptors ERalpha and ERbeta exist in beta-cells. The role of ERbeta is still unknown, yet ERalpha plays an important role in the regulation of insulin biosynthesis, insulin secretion and beta-cell survival. Activation of ERalpha by 17beta-estradiol (E2) and the environmental estrogen bisphenol-A (BPA) promotes an increase of insulin biosynthesis through a non-classical estrogen-activated pathway that involves phosphorylation of ERK1/2. The activation of ERalpha by physiological concentrations of E2 may play an important role in the adaptation of the endocrine pancreas to pregnancy. However, if ERalpha is over stimulated by an excess of E2 or the action of an environmental estrogen such as BPA, it will produce an excessive insulin signaling. This may provoke insulin resistance in the liver and muscle, as well as beta-cell exhaustion and therefore, it may contribute to the development of type II diabetes.

PLoS One. 2008 Apr 30;3(4):e2069.
Pancreatic insulin content regulation by the estrogen receptor ER alpha.
Alonso-Magdalena P, Ropero AB, Carrera MP, Cederroth CR, Baquié M, Gauthier BR, Nef S, Stefani E, Nadal A.
The function of pancreatic beta-cells is the synthesis and release of insulin, the main hormone involved in blood glucose homeostasis. Estrogen receptors, ER alpha and ER beta, are important molecules involved in glucose metabolism, yet their role in pancreatic beta-cell physiology is still greatly unknown. In this report we show that both ER alpha and ER beta are present in pancreatic beta-cells. Long term exposure to physiological concentrations of 17beta-estradiol (E2) increased beta-cell insulin content, insulin gene expression and insulin release, yet pancreatic beta-cell mass was unaltered. The up-regulation of pancreatic beta-cell insulin content was imitated by environmentally relevant doses of the widespread endocrine disruptor Bisphenol-A (BPA). The use of ER alpha and ER beta agonists as well as ER alphaKO and ER betaKO mice suggests that the estrogen receptor involved is ER alpha. The up-regulation of pancreatic insulin content by ER alpha activation involves ERK1/2. These data may be important to explain the actions of E2 and environmental estrogens in endocrine pancreatic function and blood glucose homeostasis.

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By Team FPS – February 17, 2012

How to Strain Orange Juice

https://www.youtube.com/watch?v=tgWEINd6wvs

Source – Danny Roddy

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By Team FPS – February 16, 2012

Valentine’s Day Strawberry Gummies

Recipe Source

I LOVE every day, so Valentine’s Day is a great day to reflect on matters of the heart and not of the mind. A healthy heart-shaped, heart healthy recipe version of the popular gummy was inspired by my recent interest in gelatin.

Gelatin, the cooked form of collagen, is beneficial at reducing inflammation in the body.

Most gummy items purchased at the store are sweetened with corn syrup, high fructose corn syrup, etc…and I strongly believe you should avoid all products with any corn sweeteners. This is a great recipe to try with you kids or to whip up for your loved ones all year round!

Here it is, comment with questions!

EATgredients:

  • 3 cups water, filtered
  • 1 1/2 cups NON-Hydrolyzed Gelatin (I recommend Great Lakes)
  • 3 cups sugar, organic, raw (addition by FPS – use refined white sugar)
  • ½ cup strawberries, chopped and diced
  • 2 cups orange juice, pulp-free
  • 1/4 cup lime juice, pulp-free

Directions:

1.) In medium bowl, mix water and gelatin, stirring until it forms a semi-hard substance (1 minute of stirring should be good) Let sit for 10 minutes.

2.) In medium sauce pan add sugar, orange juice, and lime juice. Mix and bring to a boil. Let boil for 2 minutes, turn off heat.

3.) Add in gelatin mix and strawberries and stir for 1-2 minutes, until there are no more clumps of gelatin. Turn off heat and cool for 5 minutes.

4.) Pour mixture in coconut oil greased pan (slightly greased). Depending on thickness of gummies you can use multiple pans/pyrex/etc…

5.) Allow to cool for 5 minutes and place in refrigerator. Gummies should be ready in an hour!

Note: I purchased the heart cut outs at Michaels for a couple of bucks!

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By Team FPS – February 15, 2012

Carbohydrate Lowers Serotonin from Exercise

Also see:
Sugar (Sucrose) Restrains the Stress Response
Gelatin > Whey
Serotonin, Fatigue, Training, and Performance
Thyroid peroxidase activity is inhibited by amino acids
Whey, Tryptophan, & Serotonin
Protective Glycine
Carbohydrate Lowers Exercise Induced Stress
Exercise Induced Stress

J Sports Sci. 1995 Summer;13 Spec No:S49-53.
Central and peripheral factors in fatigue.
Davis JM.
The causes of fatigue during muscular exercise include factors that reside in the brain (central mechanisms) as well as the muscles themselves (peripheral mechanisms). Central fatigue is largely unexplored, but there is increasing evidence that increased brain serotonin (5-HT) can lead to central (mental) fatigue, thereby causing a deterioration in sport and exercise performance. Although there are also strong theoretical grounds for a beneficial role of nutrition in delaying central fatigue, the data are much more tenuous. Dietary supplementation with branched-chain amino acids (BCAA) in low doses produces small and probably inconsequential effects on peripheral markers of brain 5-HT synthesis (plasma free tryptophan/BCAA), whereas larger doses are likely to be unpalatable, reduce the absorption of water in the gut, and may increase potentially toxic ammonia concentrations in the plasma. Alternatively, carbohydrate supplementation results in large reductions in plasma free tryptophan/BCAA and exercise time to fatigue is significantly longer, but it is difficult to distinguish between the effects of carbohydrate feedings on central fatigue mechanisms and the well-established beneficial effects of carbohydrate supplements on the contracting muscle. These data support the exciting possibility that relationships exist among nutrition, brain neurochemistry and sport performance. However, while the evidence is intriguing and makes good intuitive sense, our knowledge in this area is rudimentary at best.

Am J Clin Nutr. 2000 Aug;72(2 Suppl):573S-8S.
Serotonin and central nervous system fatigue: nutritional considerations.
Davis JM, Alderson NL, Welsh RS.
Fatigue from voluntary muscular effort is a complex phenomenon involving the central nervous system (CNS) and muscle. An understanding of the mechanisms within muscle that cause fatigue has led to the development of nutritional strategies to enhance performance. Until recently, little was known about CNS mechanisms of fatigue, even though the inability or unwillingness to generate and maintain central activation of muscle is the most likely explanation of fatigue for most people during normal daily activities. A possible role of nutrition in central fatigue is receiving more attention with the development of theories that provide a clue to its biological mechanisms. The focus is on the neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] because of its role in depression, sensory perception, sleepiness, and mood. Nutritional strategies have been designed to alter the metabolism of brain 5-HT by affecting the availability of its amino acid precursor. Increases in brain 5-HT concentration and overall activity have been associated with increased physical and perhaps mental fatigue during endurance exercise. Carbohydrate (CHO) or branched-chain amino acid (BCAA) feedings may attenuate increases in 5-HT and improve performance. However, it is difficult to distinguish between the effects of CHO on the brain and those on the muscles themselves, and most studies involving BCAA show no performance benefits. It appears that important relations exist between brain 5-HT and central fatigue. Good theoretical rationale and data exist to support a beneficial role of CHO and BCAA on brain 5-HT and central fatigue, but the strength of evidence is presently weak.

Acta Physiol Scand. 2002 Sep;176(1):65-9.
Evidence that brain glucose availability influences exercise-enhanced extracellular 5-HT level in hippocampus: a microdialysis study in exercising rats.
Béquet F, Gomez-Merino D, Berthelot M, Guezennec CY.
The relationship between brain glucose and serotonin is still unclear and no direct evidence of an action of brain glucose on serotonergic metabolism in central fatigue phenomena has been shown yet. In order to determine whether or not brain glucose could influence the brain 5-hydroxytryptamine (5-HT) system, we have monitored in microdialysis the effects of a direct injection of glucose in rat brain hippocampus on serotonergic metabolism [i.e. 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and tryptophan (TRP)], during high intensive treadmill running. The injection was performed just before and after exercise. We have shown that glucose induced a decrease of brain 5-HT levels to a minimum of 73.0 +/- 3.5% of baseline after the first injection (P < 0.01) and to 68.5 +/- 5.5% of baseline after the second injection (P < 0.01) and consequently prevented the exercise-induced 5-HT enhanced levels. We have observed the same phenomenon concerning the 5-HIAA, but brain TRP levels were not decreased by the injections. In conclusion, this study demonstrates that brain glucose can act on serotonergic metabolism and thus can prevent exercise-induced increase of 5-HT levels. The results also suggest that extracellular brain glucose does not act on the synthesis way of 5-HT, but probably on the release/reuptake system.

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By Team FPS – February 15, 2012