Evidence that pituitary adenylate cyclase-activating polypeptide is a potent regulator of fetal rat testicular steroidogenesis

Testicular steroidogenesis in the fetal rat is activated before the onset o f pituitary gonadotropin secretion, We studied here whether the pituitary a denylate cyclase-activating polypeptide (PACAP) could regulate this early L eydig cell activity. Effects of the two PACAP forms, 27 and 38, were studie d on cAMP and testosterone production of dispersed Leydig cells of embryoni c Day (F) 18.5, Furthermore, PACAP and PACAP type I receptor mRNA expressio n were measured by reverse transcription-polymerase chain reaction (RT-PCR) , and testicular PACAP concentations by RIA, The two peptides were highly p otent stimulators of fetal testes, Doses as low as 10(-18) mol/L of PACAP-2 7 and 10(-17)-10(-16) mol/L of PACAP-38 significantly stimulated cAMP and t estosterone production, with magnitude comparable to that evoked by hCG, Th ese effects were specific for fetal Leydig cells, because PACAP-responsive control cells, including murine Sertoli and granulosa cell lines, only resp onded to concentrations greater than or equal to 10(-12) mol/L, By RT-PCR, PACAP and its type I receptor mRNAs were expressed in fetal testis as early as E15.5. By Northern hybridization, PACAP mRNA was first detectable on Da y 30 postpartum and increased thereafter. Both forms of PACAP peptides were clearly detectable in E17.5 testes, with decreasing levels thereafter. In conclusion, the steroidogenesis of fetal rat Leydig cells responds to very low concentrations of PACAP, which may be an important physiological regula tor of this activity before the onset of pituitary LH secretion.