Regulation of the primate fetal adrenal gland and testis in vitro and in vivo

Abstract

In vitro experiments with the separated fetal zone (FZ) and definitive zone (DZ) of the human fetal adrenal (10–20 weeks) demonstrated ACTH stimulation of cortisol and binding in the DZ. Dehydroepiandrosterone sulfate (DHAS), produced primarily in the FZ, was stimulated inconsistently by ACTH, but consistently by hCG. Thus, the DZ appears regulated by ACTH, and the FZ principally by hCG in the first half of gestation. To assess adrenal regulation in the primate during the second half of gestation, under more physiologic circumstances, studies were carried out in a chronic fetal rhesus monkey preparation in utero in which fetuses (130–145 d gestation) were catheterized, replaced in the uterus, and the pregnancy allowed to continue up to 14 days. Dexamethasone administered to the fetus suppressed DHAS, cortisol and ACTH. Seven fetuses were challenged with ACTH. An increase in cortisol production was only observed in two; no significant stimulation was seen in the others. The challenge with ACTH was given to two infant monkeys on the first day of life. Cortisol levels increased 10-fold after ACTH stimulation. The data suggest some intrauterine factor which blocks the response to ACTH. In studies of fetal monkey testicular regulation, in vitro and in vivo, specific hCG binding was demonstrated in testicular homogenates and hCG stimulated testosterone (T) production in testicular minces. In utero intra-arterial administration of hCG to fetuses resulted in a 4-fold increase in fetal serum T. Other fetuses were challenged with bolus infusions of 10 and 50 μg gonadotropin releasing hormone (GnRH). Only the higher dose resulted in fetal T stimulation. In newborn monkeys, the lower 10 μg dose of GnRH also caused an increase in serum T. Thus, the pituitary-adrenal and pituitary-gonadal axes appear functional in the third trimester in this species, and target gland sensitivity appears to increase after birth.