Effect of mifepristone on steroid receptor expression and biotransformation of oestrogen and progesterone in rat uterus and deciduoma.

BACKGROUND: [corrected] Mifepristone is a synthetic antiprogestin which terminates early pregnancy. Since it interferes with the progesterone maintained decidua, we compared the effect of mifepristone on oestrogen and progesterone receptors, and on the biotransformation of these hormones in normal and deciduous uterus. METHODS: Ovariectomized rats were treated with an oestrogen-progesterone hormone regimen and deciduoma was induced by trauma in one horn of the rat uterus while the other served as a control under an identical hormonal milieu. Hormone receptor and biotransformation studies were done using radiolabelled oestradiol and progesterone with high specific activity. RESULTS: The artificially formed decidual tissue was comparable with that of early pregnancy. Mifepristone replenished oestrogen and progesterone receptors which were suppressed by progesterone in both the normal and decidualized uterine horns. Inhibition of oestrogen receptors by progesterone correlated with decreased oestradiol levels at the site of action. Metabolism of progesterone to less potent compounds was promoted by mifepristone. The enzymatic activities of 17beta-hydroxysteroid dehydrogenase (which metabolizes oestradiol), and 20alpha-hydroxysteroid dehydrogenase and 5alpha-reductase (which metabolize progesterone) were altered by mifepristone. CONCLUSION: The effect of mifepristone in varying the hormone receptor population and the availability of different levels of active metabolites of ovarian hormones have an Important role in the antiprogestin action of mifepristone.

Phyto-oestrogens and prostatic growth.

The incidence of and mortality from prostatic cancer in the West is higher than that in Asian countries. Migrants from Asia to western countries, who maintain their traditional diet, do not have an increased risk of prostatic cancer. This has been attributed in part to 'phyto-oestrogens' in vegetarian Asian diets. Prostatic cancer is a hormone-dependent disease and oestrogens retard the growth of prostatic tumours by interfering with the action of testosterone. Oestrogen increases the level of sex hormone-binding globulin that binds testosterone, resulting in lower free testosterone levels, thereby decreasing androgenic stimulation of the prostate. Oestrogens used to retard the growth of prostatic cancer are associated with certain undesirable side-effects. Phyto-oestrogens have weak oestrogenic potency and anticancer effects. Thus, these phytochemicals have a possible role in the prevention of hormone-dependent diseases such as prostatic cancer. Although the relative potencies of various phyto-oestrogens compared with oestradiol are low, the oestrogen receptor (ER) complexes formed byoestradiol and isoflavones have functional similarities. Also, phyto-oestrogens have a higher affinity to bind to ER-beta than ER-alpha. They are antiproliferative and inhibit tyrosine and other protein kinases which play a key role in tumorigenesis, and also inhibit the production of the potent androgen 5alpha dihydrotestosterone in the prostate. Since prostatic cancer cells usually multiply slowly and the development of this cancer can take many years before symptoms appear, the latent period provides a chemopreventive opportunity for natural therapy with phyto-oestrogens. Although phyto-oestrogens have not yet been used in long-term trials to evaluate their ability to reduce the risk of prostate carcinoma, the evidence thus far suggests that they have a protective effect against the growth of prostate tumours.