Development of the baboon fetal adrenal gland: Regulation of the ontogenesis of the definitive and transitional zones by adrenocorticotropin

Throughout gestation, the primate fetal adrenal gland is comprised of the f etal zone, which expresses the P-450 17 alpha-hydroxylase-C17,20 lyase (P-4 50c17) enzyme that catalyzes the synthesis of C-19 steroids used for placen tal estrogen production. The development of the transitional zone comprised of cortical cells that express the P-450c17 and the 3 beta-hydroxysteroid dehydrogenase-isomerase (3 beta RSD) enzymes for cortisol production, and t he definitive zone, which expresses 3 beta HSD, but not P-450c17, for miner alocorticoid synthesis, does not occur until relatively late in gestation. Although ACTH is considered essential to fetal adrenal growth and function, the role that ACTH has in the development of the transitional and definiti ve zones, is less clear. To answer this question, the width of these zones was determined by immunocytochemical expression of P-450c17 and/or 3 beta H SD in fetal adrenal glands obtained on day 100 (mid) of gestation (term = d ay 184) from baboons in which ACTH was administered to the fetus on days 95 -99 of gestation or on day 165 (late) of gestation from baboons in which fe tal ACTH was suppressed by treatment of the mother and fetus with betametha sone on days 150-164 of gestation. At midgestation, the fetal adrenal was c omprised almost exclusively of fetal zone cells and a small definitive zone (38 +/- 2 mu m in width), but was essentially devoid of a transitional zon e (7 +/- 2 mu m). Treatment with ACTH enhanced (P < 0.05) the width of the transitional zone (67 +/- 4 mu m), but not the size of the definitive zone (10 +/- 4 mu m) In late gestation, the width of the definitive zone, althou gh 2-fold greater than that on day 100, was smaller (P < 0.05) than that of the transitional zone (120 +/- 15 mu m), which greatly exceeded that at mi dgestation. Treatment with betamethasone in late gestation eliminated the t ransitional zone, but had no effect on the Size of the definitive zone (120 +/- 8 mu m). These findings indicate that the development of the baboon fe tal adrenal transitional zone late in gestation is dependent on fetal pitui tary ACTH. In contrast, the ontogenesis of the definitive zone at midgestat ion and its growth in late gestation occur in the relative absence of ACTH.