Angiotensin II receptors and inhibitory actions in Leydig cells

Rat Leydig cells possess functional high-affinity receptors for angiotensin II (AII). AII inhibits adenylate cyclase activity in Leydig cell membranes and reduces basal and human chorionic gonadotropin (hCG)-stimulated cAMP pools and testosterone production in intact cells. Treatment of cells with an inhibitory dose of forskolin (10(-9) M) and a submaximal dose of AII caused additive inhibition of hCG-stimulated events. The inhibitory action of AII was largely prevented by pertussis toxin prior to the addition of AII alone or in the presence of hCG. This study and our recent report on inhibitory action of low doses of forskolin, 10(-12)-10(-9) M (Khanum, A., and Dufau, M.L. (1986) J. Biol. Chem. 261, 11456-11459) are indicative of a pertussis toxin-sensitive subunit of adenylate cyclase available for acute regulation of Leydig cell function. 8-bromo-cAMP bypasses the inhibitory effect of forskolin as well as AII. We have, therefore, demonstrated functional AII high-affinity receptor and an acute inhibitory effect of AII on hCG action in Leydig cells. Our results have provided evidence for a pertussis toxin-sensitive guanine nucleotide inhibitory protein as mediator of the effect of AII. These findings further emphasized the importance of the cAMP pathway in the Leydig cells, and studies also suggest that tubular and locally produced AII could negatively modulate luteinizing hormone stimulation of Leydig cells.