Animal models for study of polycystic ovaries and ovarian atresia

Abstract

In the human, polycystic ovaries are generally accompanied by normal or elevated levels of serum LH, normal or slightly depressed FSH and by high levels of circulating estrogens and androgens. If the excess androgen secretion is reduced by one of several methods, ovulatory cycles are usually restored. Several animal model systems have been proposed for the study of the pathophysiology of the polycystic ovarian syndrome. These include neonatal androgenization, hCG administration to hypothyroid rats, injection of estradiol valerate and maintaining animals in constant light. In a model developed in this laboratory, pubertal or adult rats were treated with the weak androgen, dehydroepiandrosterone (DHA), to induce polycystic ovaries. This treatment also altered the blood levels of LH and FSH but the effect on gonadotropins and on the formation of the degenerative follicles was fully reversed following discontinuation of the androgen injections. The polycystic ovaries of the DHA-treated animals were steroidogenically more active than controls raising the possibility that the DHA was acting directly on the ovary in addition to an action on the pituitary-hypothalamus axis. In order to study the direct effect of androgens on the ovary, another animal model was developed in which immature, hypophysectomized rats were injected with pregnant mare serum gonadotropin (PMSG) to initiate follicular growth followed by a single injection of dihydrotestosterone (DHT). The androgen caused follicular atresia and decreased the number of ova shed in response to ovulation induction with hCG. The suppressive effects of DHT were entirely prevented by concomitant treatment with estradiol. The studies with DHT were continued using another batch of PMSG, but the DHT-induced increase in the rat of atresia and suppression of induced ovulation were no longer seen. However, when this same batch of PMSG was given with estrogen or with the antiandrogen flutamide, there was less atresia and the growth of follicles was actually enhanced. Based on these studies, it was postulated that the second batch of PMSG had greater LH activity than the first preparation and that the LH has stimulated endogenous androgen production. The ovarian follicles which appeared to be most susceptible to this DHT effect were small to medium in size and had a low capacity to synthesize estrogen. This possibility was confirmed in another animal model system in which immature rats were injected with PMSG and 4 separate injections of DHT and then sacrificed at several time points over the next 8 days.(ABSTRACT TRUNCATED AT 400 WORDS)