In vitro maturation of ovine fetal adrenal cells adenylate cyclase: Corticotropin-dependent and independent development of the response to corticotropin

Abstract

The present study investigated the corticotropin (ACTH 1–24) stimulation of cAMP production by fetal and newborn ovine adrenal cells maintained in culture for 6 days in absence or presence of ACTH 1–24. When fetal cells were exposed to ACTH 1–24 for 2 hours per day from day 1 the cAMP response to ACTH 1–24 increased during the course of the experiment to become on day 6, 40 fold higher than that observed on day 1. However, when ACTH 1–24 was continuously present in the culture medium the increase of the acute response to the hormone was weaker from day 4 onwards than in the case of cells exposed to ACTH 1–24 only for 2 hours per day. Moreover, the ACTH 1–24 stimulated cAMP production on day 6 of fetal cells cultured in ACTH-free medium for 5 days was 25 fold higher than the response obtained on day 1. When newborn adrenal cells were treated with ACTH 1–24 for 2 hours per day no significant change on ACTH 1–24 induced cAMP production during the first 4 days was observed, while continuous ACTH 1–24 treatment induced some decrease. Thereafter the hormonal responsiveness increased in both cases, but was lower in the case of continuous ACTH 1–24 treatment. Moreover, on the last day of experiment, the response of cells cultured without ACTH was 3 to 5 fold higher than that of cells treated with ACTH 1–24. These data and those reported previously (J. Steroid Biochem., 1981, 15 , 445–448 and Endocrinology, 1981, 109 , 2117–2123), suggest that during fetal life, maturation of ovine adrenal adenylate cyclase is inhibited by some factor(s). ACTH can overcome this inhibition and accelerate the spontaneous maturation of adenylate cyclase. They also suggest that the action of ACTH on both mature and fetal adrenal cells is a dichotomic process including both sensitization and desensitization, the latter being less marked in immature cells.