Vitamin E and vitamin A also protect against lipid peroxidation, and vitamin A is specifically involved in progesterone synthesis. Vitamin A also has a variety of anti-estrogen functions, that are often considered to be relevant to protection against cancer. -Ray Peat, PhD
American Journal of Clinical Nutrition, Vol 5, 666-673
Relation of Vitamin A Deficiency and Estrogen to Induction of Keratinizing Metaplasia in the Uterus of the Rat
WALTER J. BO PH.D.
Metaplasia of the uterine epithelium of estrogen-treated rats begins as many independent centers that grow and coalesce to produce a keratinized stratified squamous epithelium which replaces the original uterine epithelium.
The origin of epithelial metaplasia produced by estrogen stimulation differs from the metaplasia which occurs in vitamin A deficiency in that in the former the change takes origin in the luminal epithehium and the latter in the endometrial glands. The epithelium produced by estrogen stimulation is thicker and more heavily keratinized than that produced by vitamin A deficiency.
Keratinizing metaplasia in the uterus of the rat was observed to occur only in intact animals on a vitamin A-deficient diet or in the ovariectomized, vitamin A-deficient rats treated with estrogen. The results demonstrate that estrogen has an important role in producing keratinized epithelium in avitaminosis A and the change cannot be considered to be due to only a local vitamin A deficiency.
From the present investigation it can be concluded that vitamin A deficiency is not the primary factor in producing keratinizing metaplasia in the uterus of the rat since estrogen plays a role in producing the change.
The mode of action of vitamin A in maintaining normal uterine epithelium is not known, but it seems that a balance may exist between estrogen and vitamin A in order to maintain the integrity of the uterine epithelium and when this is disrupted keratinizing metaplasia occurs.
The Journal of Steroid Biochemistry and Molecular Biology
Volume 39, Issue 4, Part 1, October 1991, Pages 455-460
Retinoic acid acts synergistically with 1,25-dihydroxyvitamin D3 or antioestrogen to inhibit T-47D human breast cancer cell proliferation
Masafumi Koga, Robert L. Sutherland
The abnormal cornification of the vagina that occurs in vitamin A deficiency of the rat was compared with the uterine changes and it was concluded that the two are not the same. In the vagina the change is more of a hyperplastic change while in the uterus it is a true metaplasia. Therefore, the conclusions drawn from the observations made on the vagina in avitaminosis A and between vitamin A and estrogen cannot be generalized to include the uterus.
Although retinoic acid has been shown to inhibit proliferation in human breast cancer cells, the mechanisms by which these effects are mediated are not known. Since several steroid hormones and their synthetic antagonists also inhibit proliferation of human breast cancer cells, we investigated the interactions between retinoic acid, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and antioestrogens in the control of human breast cancer cell proliferation in vitro. When T-47D cells, the most sensitive of six human breast cancer cell lines to the growth inhibitory effects of retinoic acid, were treated with retinoic acid and 1,25-(OH)2D3, a synergistic inhibitory effect on cell growth was observed. Retinoic acid also enhanced the growth inhibitory effect of various antioestrogens (4-hydroxytamoxifen, 4-hydroxyclomiphene or LY117018). However, retinoic acid did not affect oestradiol-induced growth stimulation. Measurement of the cellular receptors for 1,25-(OH)2D3 and oestrogen revealed no significant change in receptor levels following treatment with concentrations of retinoic acid which modulated growth.
These results indicate that retinoic acid not only has direct growth inhibitory effects on breast cancer cell proliferation but also augments the effects of some other known regulators of breast cancer cell replication including 1,25-(OH)2D3 and antioestrogens. Synergism appears to involve interactions with steroid hormone action distinct from changes in steroid hormone receptor levels.