EFFECT OF DECAPITATION AND CHRONIC INVIVO TREATMENT WITH A GONADOTROPIN-RELEASING-HORMONE AGONIST ON TESTICULAR STEROIDOGENESIS IN THE RAT FETUS

To study the effect of in-vivo gonadotrophin-releasing hormone (GnRH) treatment on testicular testosterone production during late fetal life in the rat, 18.5-, or 20.5-day-old fetuses were decapitated and injected with either long-acting microcapsules containing the GnRH agonist D-Trp-6-GnRH or vehicle only. Two days later, fetal and maternal plasma was collected and fetal testes were removed and incubated for 6 h in medium with either 100 ng LH/ml or without LH. The GnRH agonist concentrations in the plasma of GnRH-treated decapitated male fetuses were comparable in the two age-related groups (5 nmol/l). After treatment of the fetus with D-Trp-6-GnRH, the agonist was recovered in maternal plasma, showing that this peptide can cross the fetal-maternal barrier. In 22.5-day-old decapitated vehicle-treated male fetuses, the plasma testosterone level dropped to that observed in control female fetuses, and treatment of decapitated male fetuses with the GnRH agonist did not further reduce it. At both days 20.5 and 22.5, basal in-vitro testosterone secretion by testes from decapitated vehicle-treated fetuses was lower than secretion by testes from intact control fetuses from the same litter, but LH-stimulated secretion was similar in both groups. Both basal and LH-stimulated secretion by testes from GnRH-treated decapitated fetuses was lower than secretion by testes from vehicle-treated decapitated fetuses and larger reductions were measured on day 22.5 than on day 20.5 (-48 vs -18% for basal secretion, and -76 vs -40% for LH-stimulated secretion). These results suggest that, in contrast to immature Leydig cells, fetal Leydig cells are not desensitized to gonadotrophic stimulation after hypophysial deprivation, and that, in the rat, a negative testicular response to a putative intratesticular GnRH or to some other factor using the same intracellular pathway is established during late fetal life.