Stimulation of the andorgen pathway occurs mainly through cAMP mediated mechanism. The stimulatory event can be negatively influenced by the action of certain hormones. In recent studies we have demonstrated the presence functional angiotensin II (AII) receptors in the Leydig cell of high affinity Ka 1.7 nM and low capacity 2,000 sites per cell. AII inhibits GTP and LH sitmulated adenylate cyclase in Leydig cell membranes. This hormone also acutely inhibits LH stimulation of cyclic AMP pools and testosterone production in Leydig cells. These effects were prevented by incubation with pertussis toxin and reversed by 8- bromo cAMP additions indicating that AII actio in the Leydig cell occurs through the guanyl nucleotide inhibitory unit of adenylate cyclase (Gi), findings that have further emphasized the importance of the cAMP pathway in the Leydig cell. In addition to the potentiation and direct stimulatory effect of forskolin, a dose-dependent inhibitory effect of forskolin (ID50, pM) on basal and hCG-stimulated cyclic AMP pools and testosterone production were demonstrated through inhibition of adenylate cyclase via direct or indirect activation of Gi. High affinity action of forkolin is of value for direct evaluation of functional Gi activity. Unlike the adult Leydig cell, the fetal and immature cell are refractory to desensitization and maintain up-regulated LH receptor and steroidogenic functions, and their inability to be desensitized by gonadotropin is attributed to the absence of an estrogen-mediated regulation of the androgen pathway. The fetal testis possess in addition to the predominant fetal cell population a small population of transitional cells with functional capacities of the adult cell. After appropriate treatment of fetal cultures (i.e. estrogen, and frequent or a high gonadotropin dose) emerge a functional adult-like cell type from the fetal Leydig cell population. The cultured fetal Leydig cell system provides a useful model to elucidate LH, GnRH action, beta-endorphin regulation and the mechanism involved in the development of gonadotropin-induced estradiol-mediated desensitization of steroidogenesis.
