ONTOGENY OF THE INVITRO RESPONSE OF RAT TESTIS TO GONADOTROPIN-RELEASING-HORMONE

The age-related evolution of the in vitro effects of a gonadotropin releasing hormone agonist ([D-Trp6]-GnRH) on the secretion of testosterone by the testis, cultured during 3 days on a Millipore filter floating on M199 medium, was studied during the perinatal period in the rat. The basal and luteinizing hormone (LH)-stimulated secretions by testes explanted on fetal day 14.5 were unaffected by the agonist. With fetal testes explanted on days 16.5 and 18.5 post-conception, the agonist inhibited, in a concentration-dependent manner, both basal and LH-stimulated secretions from the second or the third day of treatment onwards. With fetal and neonatal testes explanted on days 20.5, 21.5 and 31.5 post-conception, the GnRH agonist also had a long-term inhibitory effect on LH-stimulated secretion, but increased basal secretion. This stimulatory effect was already observed after 4 h of culture, and was maintained for 3 days. These results suggest that, during fetal development, the cellular mechanisms involved in the negative testicular response to GnRH are differentiated 3-5 days before those involved in the positive response. Lastly, after 3 days of preculture in hormone-free medium, fetal testes explanted on day 14.5 displayed long-term GnRH agonist inhibition of in vitro basal secretion of testosterone. This observation points out a spontaneous differentiation of the negative responsiveness to GnRH in the cultured fetal testis.