Gonadotropin-independent regulation of steroidogenesis in the fetal rat testis.

UNLABELLED: The goal of the present study was to determine whether the onset of fetal Leydig cell steroidogenesis is dependent on gonadotropic stimulation. The relationships between the onset of pituitary LH synthesis and secretion, and the response of testicular steroidogenesis to LH and various putative paracrine factors were examined. We found by reverse transcription-polymerase chain reaction (RT-PCR) that the LHbeta-subunit gene expression in the fetal pituitary gland starts on embryonic day (E) 16.5. Plasma LH was very low (< 5.0 ng/L) until E19.5 and increased significantly thereafter. In contrast, the greatest increase in the testicular testosterone had already occurred between E18.5 and E19.5. Hence, fetal testicular steroidogenesis must start independent of LH stimulation. Basal testosterone production in incubations of fetal testis (E16.5-19.5) was high, 50-80% of the hCG-stimulated level. In contrast, in dispersed fetal Leydig cells, basal steroidogenesis was consistently low. This suggests the presence of paracrine factors in the intact testes that stimulate their steroidogenesis. Effects of various putative paracrine factors were thereafter tested on the fetal testis. We found for the first time that both vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP-27) markedly stimulated fetal, but not adult, Leydig cells. IN
CONCLUSION: 1) Pituitary LH cannot be the initial stimulus for fetal testicular steroidogenesis. 2) Some paracrine factor(s) probably turn on and maintain early fetal testicular steroidogenesis before the later onset of LH secretion, although a constitutive component in the onset of steroidogenesis is also possible. 3) VIP and PACAP-27 are likely candidates for a paracrine stimulus of the fetal testis.