ACTH induction of the maturation of ACTH-sensitive adenylate cyclase system in the ovine fetal adrenal

Abstract

The number of ACTH receptors and the adenylate cyclase (AC) responsiveness to several stimuli have been measured in adrenal crude membranes from 120-day-old control ovine fetuses and from fetuses which were perfused in utero for 5 days with ACTH 1–24 (0.1 mg/day). The response of AC to ACTH 1–24, ACTH 1–24 + Gpp(NH)p ∗ ∗ Guanosine (β,γ-imido) triphosphate. , Gpp(NH)p and NaF was significantly higher in ACTH 1–24 treated fetuses than in control animals. The number of ACTH receptors was also enhanced by the ACTH 1–24 perfusion. These changes were correlated with an increased potency of isolated adrenal cells from ACTH 1–24 treated fetuses to produce cAMP and corticosteroids when stimulated in vitro by ACTH 1–24 or cholera toxin. Metyrapone (300 mg/day) perfused for 4 days in 139-day-old fetuses increased plasma ACTH levels above control values. This treatment significantly enhanced the number of ACTH receptors and the AC responsiveness to the hormone without changing the stimulation induced by Gpp(NH)p and NaF. Since the changes prematurely induced by ACTH appear similar to those which spontaneously occur during late gestation, it is suggested that ACTH is the main factor involved in the prepartum adrenal maturation of the fetus.