The hormonal control of gonadal endocrine function is studies in ovarian and testicular target cells. In the ovary, the FSH-stimulated granulosa cell is a model of hormone-induced cellular differentiation. In cell cultures, FSH causes early and delayed increases in cAMP production, with induction of peptide hormone receptors (LH, Pr1) and steroidogenic activity from 18-24 hr of culture. During FSH action, the RNA and protein required for differentiation were synthesized largely during the second day of culture, and endogenously produced estrogen was found to be essential for the full expression of LH receptors. Granulosa cell maturation is induced by cAMP generators such as choleragen and forskolin, and is modified by GnRH, EGF, PDGF, adenosine, calcium agents, and estrogens. Most of these agents act relatively rapidly to influence granulosa-cell differentiation, but their effects are largely manifested during the second day of culture. Inhibition of granulosa cell maturatiion by GnRH is highly calcium-dependent, similar to its stimulatory action in the pituitary, and is related to elevation of cytosolic calcium. GnRH also attenuates the FSH-induced rise in Type II protein kinase, initially decreasing enzyme activity and later reducing the synthesis of the RII cAMP-binding subunit. Protein kinase C was identified in granulosa cells and shown to phosphorylate several cytosolic proteins. In the adult testis, GnRH receptor blockade decreased Pr1 receptors and testosterone production but did not alter the desensitization response to exogenous gonadotropin, showing that testicular GnRH does not mediate the down-regulating effects of elevated gonadotropin on testicular function. The neonatal rat testis was found to be relatively immune to the inhibitory effects of estrogen, and to show largely positive responses to elevations in plasma gonadotropins and PRL, instead of the receptor loss and desensitization seen in the adult. These features of the fetal- neonatal population of Leydig cells may serve to ensure optimal androgen production during the critical period of sexual differentiation.
