Abstract

PIP: This progress report dealing with novel peptides in ovarian follicular fluid and the implications for contraceptive development includes a description of a new "morphology" of the ovarian follicle and a review of the interrelationships of ovarian microscopic morphology and gonadotropin receptors, and ovarian secretion of steroids. The specificity of the factors examined, and their presumed localization of action, suggest several new targets for contraception. If the LH (luteinizing hormone) surge were prevented from inducing withdrawal of OMI (oocyte maturation inhibitor) from the oocyte in the dominant follicle, all of the endocrine events of the cycle would occur, but the oocyte would not be viable. Injection of OMI in such a way as to reach the oocyte during the time when the surge is taking place could prevent resumption of meiosis. The ovarian GnRH (gonadotropin releasing hormone) receptors are a prime target for contraception. They seem to be the conduit through which GnRH and its agonists can suppress steroidogenesis, ovulation, and corpus luteum function. Such agonists working via the pituitary gland can lead to indirect suppression of ovarian function, through down regulation of GnRH receptors within the pituitary and subsequent failure of LH and FSH (follicle stimulating hormone) secretion. Antagonistic analogues to GnRH can block pituitary gonadotropin secretion, resulting in suppression of LH and FSH. Timed administration of GnRH agonists or antagonists can block ovulation, follicular development, or corpus luteum function, depending on when during the cycle administration occurs. While GnRH agonists can cause luteolysis via LH withdrawal from normal corpora, it might be feasible to prevent the induction of LH receptors in the 1st place. A complex cascade of events lies between secretion of GnRH and action of LH and FSH on the ovary. The receptor binding inhibitors to LH and FSH could provide local interfering agents that would prevent gonadotropin regulation of ovarian function. The most specific suppressing agent for FSH that has been used is folliculostatin. It can prevent FSH secretion in male recipients and could be used as a block for spermatogenesis.