Date of Award
Doctor of Philosophy (PhD)
Gerald J. Pepe
Reinhart B. Billiar
Russell L. Prewitt
R. James Swanson
The present study determined whether the growth of, as well as ACTH receptor and P-450 enzyme messenger ribonucleic acid and/or protein levels in the baboon fetal adrenal are dependent upon fetal pituitary ACTH during mid and late gestation and the mechanism by which placental estrogen modulates ACTH actions. Administration of betamethasone (3mg/day) to baboon mothers on days 60-99 of gestation and to the fetus (0.6 mg/, n = 4) or to the fetus (0.6mg) and mother (6 mg/ml; n = 4) every other day between days 150-164 of gestation (term = 184 days) decreased (P $53β-hydroxysteroid dehydrogenase-isomerase (3β-HSD(+)ctochrome P450 17α-hydroxylase, 17/20-lyase (P450c17) to the definitive zone (3βHSD (+), P450c17 (-)), transitional zone (3-β (+) and P450c17 (+)), and fetal zone (P450c17 (+), 3β-HSD (-)). At term, betamethasone treatment resulted in a reduction in the size of the fetal zone and eliminated the transitional zone. However, the definitive zone although reduced in size was maintained in betamethasone-treated animal. These data indicate that ACTH induces the differentiation of the transitional zone and thus the potential for the fetal adrenal to synthesize cortisol.
To test the hypothesis that estrogen modulates the role of ACTH on fetal adrenal development, the aromatase inhibitor CGS 20267 was administered to baboon mothers between days 100 and 164 of gestation (n = 3). CGS treatment suppressed maternal and fetal peripheral serum estradiol to less than 2% of control levels, and enhanced (P< 0.05) fetal adrenal weight by 75% but decreased fetal cortical cell size. In contrast, the intensity and immunoexpression of P450c17 was enhanced and present in virtually all cells. We conclude that the ontogenic development of the fetal adrenal is prevented in estrogen-depleted baboons. Simultaneous administration of CGS and estrogen restored all aspects of fetal adrenal development. To test if estrogen-mediated modulation of adrenal development reflected a direct action of estrogen, we determined whether the adrenal expressed the estrogen receptor (ER). At term ER was observed in the definitive zone adjacent to the capsule but was not observed in either transitional or fetal zone cells. Treatment with CGS or CGS and estrogen had no effect on the ER expression. Betamethasone treatment, increased the intensity and width of the zone of cells expressing the ER. The betamethasone effect may be mediated by a glucocorticoid receptor (GR) which was detected in both the definitive and fetal zones. The results of the present study demonstrated that reduced placental estrogen appears to enhance preferentially ACTH-induced growth of the adrenal fetal zone preventing the formation of the definitive zone, while having no significant effect on ER expression of the definitive zone.
Leavitt, Maria G..
"Interaction of ACTH and Estradiol in the Regulation of Growth, Differentiation, and Steroidogenic Maturation of the Baboon Fetal Adrenal Gland"
(1997). Doctor of Philosophy (PhD), Dissertation, , Old Dominion University, DOI: 10.25777/v4an-2g93