Biochemical modifications involved in the maturation of the ovine fetal adrenal gland in late gestation: their modalities and regulation.

During the last month of intra-uterine life, the steroidogenic response of the ovine fetal adrenal glands to ACTH increases and becomes maximal at the time of birth. This development involves modifications at different steps of the adrenocorticotropic hormone (ACTH) action mechanism. It has been shown that the enhanced capacity of the cells to produce cAMP is related to at least three factors: an increased number of ACTH receptors, increased activity of the Ns subunit of adenylate cyclase, and enhancement of guanosine 5'-triphosphate (GTP) availability. The ability to produce pregnenolone and the activity of both 3 beta-hydroxy steroid dehydrogenase/isomerase and 17 alpha-hydroxylase are mainly enhanced in the steroidogenic pathway. The infusion of ACTH for 5 days into 115 to 120-day old fetuses results in the development of most of these biochemical process. Similarly, ACTH can induce maturation of cultured fetal adrenal cells and some other proopiomelamocortin (POMC)-derived peptides can potentiate its acute steroidogenic activity in vitro. However, even in the absence of ACTH, the adenylate cyclase system and the steroidogenic potency of cultured cells increase but to a lesser extent than when ACTH is present in the culture medium. It is suggested that ACTH is the main trophic hormone of the ovine fetal adrenal during the last month of gestation, even if other stimulatory factors may also be important. The in vivo maturation of ovine fetal adrenal is blocked by the presence of some unknown inhibitory factors in the fetal circulation which are of likely extrapituitary origin.