The hormonal control of gonadal endocrine function by gonadotropins and growth factors is studied in ovarian and testicular target cells. In the ovary, the mechanisms of hormonal control of granulosa-cell maturation, and the production of specific receptors and other proteins that mediate hormone action in cells of the reproductive system, were analyzed in cultured granulosa cells. Studies with estrogen antagonists showed that the cAMP-mediated production of LH receptors in FSH-stimulated granulosa cells, demonstrated in earlier studies, was dependent upon the continued actions of estrogen throughout the maturation process. In addition, the ability of aromatase inhibitors to prevent LH receptor expression revealed that sustained production of estrogen by the maturing target cells was essential for FSH-induced granulosa cell differentiatioon. The inhibitory action of GnRH on ovarian function was found to be reproduced by activators of protein kinase C, indicating that this enzyme has a major role in GnRH action in the ovary as well as in the pituitary gland. In immature granulosa cells, phorbol esters suppressed FSH-induced aromatase activity and cellular aggregation and caused translocation of protein kinase C from cytosol to other cellular compartments. Synthetic diacylyglycerols also prevented FSH-induced LH receptor expression and progesterone production, but had less inhibitory effect than phorbol esters on cell aggregation and aromatase activity, and did not cause redistribution of protein kinase C. The prominent suppression of granulosa cell differentiation by phorbol esters reflects their rapid and prolonged action on protein kinase C. In contrast to such inhibitory effects in the immature granulosa cell, activation of protein kinase C in more differentiated cells caused stimulation of cyclic AMP formation and progesterone synthesis. Thus, in the mature granulosa cell the calcium, phospholipid-dependent enzyme is also involved in the regulation of esteroidogenesis by hormonal ligands including gonadotropins and GnRH.
