Interactions among endocrine control systems in the regulation of ovarian function

During sequential physiologic maturation of an individual follicle, the number of granulosa cells increases in excess of 1000-fold, while intra-ovarian concentrations of sex steroids escalate by 100-fold. The recent development of several in vitro ovarian systems has permitted a more extensive and direct assessment of specific mechanisms that control growth and steroidogenesis in granulosa and thecal cells. For example, estradiol and follicle stimulating-hormone seem to promote the production by ovarian cells of low-molecular-weight growth factors, that may participate in granulosa cell proliferation. Luteinizing hormone stimulates the de novo synthesis of prostacyclin by granulosa cells in vitro. Prostacyclin, in turn, may regulate the microvasculature of the maturing follicle and directly stimulate steroidogenesis. The effects of individual hormones are markedly modified by other intraovarian endocrine factors, and by the precise status of cytodifferentiation of the ovarian cells. For example, the actions of prolactin on granulosa-cell steroidogenesis are influenced strikingly by both agonistic and antagonistic interactions between prolactin and estradiol, as well as by the level of granulosa-cell cytodifferentiation attained in vivo. Similar bihormonal intrafollicular interactions are recognizable between estrogen and follicle-stimulating hormone in the early follicle, and between estradiol and luteinizing hormone in the maturing follicle. These interactions are susceptible to more precise examination under defined in vitro conditions. Overall, recent advances in biomedical research continue to elucidate basic molecular mechanisms of hormone action in ovarian cell physiology. Such advances are likely to continue to provide important insights into the pathophysiology of clinical disorders of human reproduction.