Ontogeny of the ACTH receptor, adenylate cyclase and steroidogenesis in adrenal.
The steroidogenic responsiveness to ACTH of the fetal adrenal gland of several species increases strikingly during the last weeks of gestation. Using the ovine fetus model it has been shown that this spontaneous development involves modifications at different steps in the mechanism by which ACTH stimulates the cells: one located at the cell membrane, another beyond cAMP formation, namely, in the steroidogenic pathway. The first phenomenon is related to at least three processes: an increased number of ACTH receptors, an increased activity of adenylate cyclase, and an enhanced coupling of these entities. The enhanced steroidogenic capacity is related mainly to an increased ability to produce pregnenolone and to an enhanced activity in both 3 beta-hydroxysteroid dehydrogenase and 17 alpha-hydroxylase. Infusion of 115-120-day-old fetuses with ACTH for only 5 days induced development of most of these biochemical steps, indicating that ACTH is an important regulating hormone for the maturation of fetal adrenocortical function. However, when ovine fetal adrenal cells were cultured in the absence of ACTH, there was a spontaneous development of the hormone-sensitive adenylate cyclase system and of the steroidogenic pathway. Addition of ACTH to the culture medium accelerated and further enhanced these maturation processes. These results suggest that the in vivo maturation of ovine fetal adrenal is blocked by the presence in the fetal circulation of some inhibiting factors which are likely to be of extrapituitary origin. Therefore, the 'maturation' of ovine fetal adrenocortical function appears to be regulated in a coordinate fashion by stimulatory, ACTH and unknown inhibitory factors.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000311:Adrenal Glands / Q000196:embryology / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D005260:Female; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018043:Receptors, Corticotropin; D012756:Sheep; D013256:Steroids / Q000096:biosynthesis*
D011956:Receptors, Cell Surface; D018043:Receptors, Corticotropin; D013256:Steroids; D000262:Adenylyl Cyclases