Reproductive capacity in mammals results from physiologic interplay between steroid hormones produced by the gonads and peptide hormones secreted by the anterior pituitary gland and brain. Clinical manipulation of these interactions can eventuate in fertility's induction or blockage. We examine cellular and molecular mechanisms underlying gonadal steroid regulation of the secretion of the gonadotropic hormone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) by the adenohypophysis and of gonadotropin-releasing hormone (GnRH) by the brain. This feedback regulation establishes the temporal and quantitative parameters of hypophysial gonadotropin secretion necessary for normal gonadal development and function.

Primarily, we monitor the direct actions of estrogens, progestins, and androgens by studying the physiology of rat gonadotrophs in cell culture. To date, we have characterized temporally the direct actions of androgens, estrogens, and progestins in gonadotropin synthesis and secretion, and we have tested for their influences on the intracellular effector systems implicated in GnRH-stimulated exocytosis. The magnitude of their responses correlates closely with the number of nuclear steroid-receptor complexes in the cell. In contrast, steroidal metabolism by local reductases and dehydrogenases is not obligatory for the expression of their actions. We are characterizing how these steroids modulate the glycosylation, and, thus, the bioactivity, of secreted and stored LH and FSH. Other studies involve quantifying changes in gonadotropin release by individual cells using a reverse hemolytic plaque assay and attempting to detect cell components whose level or isoform distribution is influenced by steroidal and GnRH treatment.