Reversal of the Effects of Anti-Oestrogens and Norethynodrel on Gonadotrophin-Induced Ovulation in Rats

Abstract

The oral administration of 0\m=.\5 mg/kg of U11555A or MRL-41 induced superovulation in the pms-treated immature rat. This effect was prevented by the injection of 16 mg/kg of sodium phenobarbital 15 min prior to the expected release of endogenous lh. It was postulated that the superovulatory action of low doses of these anti-oestrogens was mediated through stimulation of lh secretion via antagonism of endogenous oestrogen. Conversely, higher doses of U11555A (6 mg/kg) or MRL-41 (3 mg/kg) suppressed ovulation; similar effects were produced by norethynodrel (40 mg/kg). However, the injection of hcg reversed the inhibitory effects of these agents on ovulation. These results suggested that higher doses of U11555A or MRL-41 and norethynodrel interfered with either the release of lh and/or the subsequent ovarian response.

Pharmacologic alteration of steroid hormone functions

“…However, in higher doses these substances will block ovulation. 23 Another possible antifertility mechanism is antagonism of the "estrogen surge" which occurs prior to implantation in rats. 33 , 34, 64, 136 The hamster appears to be more resistant than the rat to the antifertility effects of estrogen antagonists, 35 possibly because an estrogen surge may not be required for implantation.…”

The Action of Clomiphene in the Ewe

“…Barnes & Meyer (1962) presented evidence that clomiphene inhibits secretion of gonadotrophin and ovulation in adult rats. More recently, Coppola & Perrine (1965) and Coppola, Leonardi & Ringler (1966) have shown that, while higher doses (1-5 mg/kg/day) inhibit ovulation, lower doses (0-5 mg/kg/day) stimulate gonado¬ trophic activity. Even at the higher doses, these authors observed "intense follicular stimulation" and presumed the absence of corpora lutea to be due to inhibition of release of lh.…”