A ROLE FOR EPIDERMAL GROWTH-FACTOR IN THE MORPHOLOGICAL AND FUNCTIONAL MATURATION OF THE ADRENAL-GLAND IN THE FETAL RHESUS-MONKEY IN-VIVO

We determined the effects of epidermal growth factor (EGF) and beta-me thasone on the growth and development of the adrenal gland of the feta l rhesus monkey in vivo between 121-128 days of gestation. The adrenal to body weight ratio was significantly greater (P < 0.05) in EGF-trea ted fetuses (0.988 +/- 0.046 x 10(-3) g/g) and significantly reduced ( P < 0.05) in beta-methasone-treated fetuses (0.401 +/- 0.056 x 10(-3) g/g) compared with that in control fetuses (0.689 +/- 0.050 x 10(-3) g /g). The increase in adrenal weight with EGF administration was due to hypertrophy of definitive zone cells of the adrenal cortex, whereas t he reduction in adrenal weight after beta-methasone treatment was due to a decrease in the size of definitive and fetal zone cells of the ad renal cortex. By Western analysis, EGF treatment induced a significant (P < 0.05) 2.8-fold increase in the amount of protein for B beta-hydr oxysteroid dehydrogenase/isomerase (3 beta HSD) in the fetal adrenal. EGF also stimulated the induction of immunocytochemical staining for 3 beta HSD in transitional zone cells of the adrenal cortex. In contras t, beta-methasone resulted in 2.6-, 4.5-, and 6.6-fold significant dec reases (P < 0.05) in the amount of protein for cytochrome P450 cholest erol side-chain cleavage, cytochrome P450 17 alpha-hydroxylase/17,20-l yase, and 3 beta HSD in the fetal adrenal. After beta-methasone treatm ent, 3 beta HSD staining was detected in some of the definitive zone c ells, with no 3 beta HSD staining in the transitional zone. In conclus ion, growth and functional differentiation of fetal primate adrenal gl and can be accelerated prematurely by EGF and inhibited by glucocortic oid negative feedback.