Changes in the binding of oestradiol to uterine oestrogen receptors induced by some progesterone and 19-nor-testosterone derivatives

Abstract

The effects of two progesterone derivatives, namely medroxyprogesterone acetate (MPA) and chlormadinone, and two 19-nor-testosterone derivatives, namely norgestrel and norethisterone, on the binding of oestradiol to its cytoplasmic receptors in the rat uterus were compared. In experiments performed in vivo, the rats were given a single oral dose (15 mg/kg) of one of the four progestins and killed 1, 6, 24 and 48 h later. Norgestrel, norethisterone and MPA induced a prompt and remarkable decrease in oestradiol-receptor interaction 1 h after treatment. This reduction lasted almost unchanged for 24 h in rats treated with MPA or norgestrel, but was much lower in animals given norethisterone. In the hours that followed, the effect of MPA and norgestrel began to decrease, but was still detectable after 48 h, whereas the effect of norethisterone had disappeared by this time. The effect of chlormadinone was much less than that induced by both MPA and norgestrel 1, 6 and 24 h after treatment. On the other hand, this effect was less than that caused by norethisterone 1 h after administration, equal after 6 h and much greater after 24 and 48 h. In experiments performed in vitro, the different ability of the four progestins to interfere with the capacity of oestradiol to bind to its receptors was confirmed. In conclusion, all the synthetic progestins used were able to reduce the binding of oestradiol to its cytoplasmic receptors, although there was a clear difference between the progestins in the intensity and duration of this effect. This could be one of the mechanisms by which progestins modulate the activity of oestrogens in target tissues.

Medroxyprogesterone acetate inhibits the cardioprotective effect of estrogen in experimental ischemia-reperfusion injury

“…7 MPA also has antagonistic properties at glucocorticoid receptors, leading to an increased ability of human leukocytes to express the adhesion molecule ICAM-1. 6 The binding of E to its receptors is also reported to be inhibited by MPA, 43 and progestogens like MPA are reported to down-regulate the E receptor in target tissues. 42,44 Complete inhibition of E binding to its receptors seems an unlikely explanation for the observations in the present study, as this would also have limited the effects of E on the body weight and uterine proliferation, unless E receptors in cardiovascular target tissue are down-regulated at a lower concentration of MPA than that required in other target tissues.…”

A phase plane graph based model of the ovulatory cycle lacking the "positive feedback" phenomenon

“…Based on reports on various estrogen and progesterone target tissues (human uterus [21], endometrial hyperplasia [22,23], rat hypothalamic and limbic nuclei [24], anterior pituitary of rats [25,26], target organs in the female rat [27-29]), it is here proposed that without binding of various ER ligands (estradiol (E2) and probably some estrone (E1) locally converted from androgens), PgR expression remains low in pituitary and hypothalamus.…”

Effect of Single-Dose Progesterone Administration on Estradiol Receptor Levels in Normal Human Endometrium

“…Progesterone, the physiological modulator of estrogen activity on target cells [1][2][3], caused a selective decrease of the occupied form of the nuclear estradiol receptor (RnE2) in rat and proestrus hamster uterine tissues following acute administration [4]. This ef fect did not depend on pretreatment levels of the cytosolic estradiol receptor (RcE2) or of plasma estradiol.…”