Estrogen-like effects of norethisterone on the hypothalamic pituitary unit of ovariectomized rats

The acute and chronic effects of norethisterone (NET) upon gonadotropin dynamics were studied in long-term ovariectomized adult Wistar rats. Time course studies showed that plasma LH declined within 1 h following a single NET sc injection and remained low for the next 4 h duration of the experiment. Pre-treatment with tamoxifen prevented the acute anti-gonadotropic effect of NET and GnRH administration to NET treated rats resulted in an abolishment of the pituitary responsiveness in terms of LH. Chronic administration of NET but not progesterone to castrated animals induced a significant decrease of plasma and pituitary LH with a concomitant replenishment of hypothalamic GnRH in an identical fashion to that observed with chronic administration of 17 beta-estradiol. Furthermore, administration of NET and 17 beta-estradiol but not progesterone diminished the number of GnRH pituitary binding sites to levels found prior castration. These results indicate that the effects of this 19-nor synthetic progestin upon gonadotropin modulation in the long-term gonadectomized rat do not resemble those of progesterone and suggest that NET is acting through different mechanisms. The data are consistent with an estrogen-like mode of action.