GONADOTROPIN-INDEPENDENT REGULATION OF STEROIDOGENESIS IN THE FETAL-RAT TESTIS

The goal of the present study was to determine whether the onset of fe tal Leydig cell steroidogenesis is dependent on gonadotropic stimulati on. The relationships between the onset of pituitary LH synthesis and secretion, and the response of testicular steroidogenesis to LH and va rious putative paracrine factors were examined. We found by reverse tr anscription-polymerase chain reaction (RT-PCR) that the LH beta-subuni t 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 increas ed 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 tes tis (E16.5-19.5) was high, 50-80% of the hCG-stimulated lever, In cont rast, in dispersed fetal Leydig cells, basal steroidogenesis was consi stently low. This suggests the presence of paracrine factors in the in tact testes that stimulate their steroidogenesis. Effects of various p utative paracrine factors were thereafter tested on the fetal testis. We found for the first time that both vasoactive intestinal peptide (V IP) and pituitary adenylate cyclase-activating polypeptide (PACAP-27) markedly stimulated tal, but not adult, Leydig cells. In conclusion: 1 ) Pituitary LH cannot be the initial stimulus for fetal testicular ste roidogenesis, 2) Some paracrine factor(s) probably turn on and maintai n early fetal testicular steroidogenesis before the later onset of LH secretion, although a constitutive component in the onset of steroidog enesis is also possible, 3) VIP and PACAP-27 are likely candidates for a paracrine stimulus of the fetal testis.