Time-related effects of arginine vasopressin on steroidogenesis in cultured mouse Leydig cells

The dose and time treatment effects of arginine vasopressin (AVP) on basal and hCG-stimulated testosterone accumulation by purified mouse Leydig cells in primary culture were examined. Pretreatment for 24 h of Leydig cells with AVP caused a stimulation of the acute (3 h) basal testosterone accumulation. In these conditions, progesterone accumulation was also increased. The stimulatory effect of AVP (10(-11)-10(-5) M) on testosterone accumulation was dose-dependent and as little as 10(-11) M-AVP caused significant stimulation whilst maximal effect was achieved with 10(-7) M. Oxytocin (10(-6) M) also showed a stimulation of testosterone accumulation in basal conditions, but the other peptides tested at the same concentration (neurotensin, somatostatin and substance P) did not have any effect. When Leydig cells were exposed to AVP for a longer period (48 or 72 h), the increase in basal testosterone accumulation disappeared. AVP treatment of Leydig cells for 72 h led to a significant and dose-dependent reduction in the hCG-responsiveness without altering the slope of the hCG dose-response curve. This inhibitory effect, which was also observed when AVP-pretreated Leydig cells were acutely challenged for 3 h with 8-bromo-cAMP, was accompanied by a concomitant increase in progesterone accumulation. These results indicate that AVP can exert a dual effect on mouse Leydig cells: stimulatory on basal testosterone accumulation during short-term exposure (24 h) and inhibitory on the response to hCG stimulation after long-term treatment (72 h). They provide additional evidence that neurohypophysial peptides directly affect Leydig cell steroidogenesis.