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Original Studies |
Departments of Obstetrics/Gynecology/Reproductive Sciences and Physiology, Center for Studies in Reproduction, University of Maryland School of Medicine (G.W.A., E.D.A.), Baltimore, Maryland 21201; and the Department of Physiology, Eastern Virginia Medical School (M.G.L., G.J.P.), Norfolk, Virginia 23507
Address all correspondence and requests for reprints to: Eugene D. Albrecht, Ph.D., Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Bressler Research Laboratories 11019, 655 West Baltimore Street, Baltimore, Maryland 21201.
Although fetal pituitary ACTH is important to fetal adrenal growth and
steroidogenesis in the second half of primate pregnancy, its role in
adrenal development and function has not been established in
vivo in the first half of gestation. In the present study,
therefore, baboons were treated at midgestation with betamethasone to
determine the effect of fetal pituitary ACTH on fetal adrenal growth,
development, and ACTH receptor and P-450 enzyme messenger ribonucleic
acid (mRNA) levels. The administration of betamethasone to baboon
mothers on days 6099 of gestation (term = 184 days) decreased
fetal pituitary POMC mRNA levels by 54% (P <
0.01) and fetal serum ACTH levels to undetectable values
(P < 0.05). The decline in ACTH was associated
with decreases in fetal adrenal weight (P <
0.001), cortical cell size (P < 0.05), appearance
of apoptosis and cellular disorganization, and a loss of
immunocytochemically demonstrable definitive zone-specific
5-3ß-hydroxysteroid dehydrogenase expression. The
concomitant administration of ACTH and betamethasone restored these
aspects of adrenal integrity to normal. Moreover, there was
approximately a 95% decrease (P < 0.01) in fetal
adrenal expression of ACTH receptor, P-450 cholesterol side-chain
cleavage, and P-450 17
-hydroxylase 17/20-lyase mRNA levels after
betamethasone administration. We conclude that fetal pituitary ACTH is
necessary for the growth and development of fetal and definitive
cortical zones and the marked coordinated increase in ACTH receptor and
maintenance of P-450 cholesterol side-chain cleavage/P-450
17
-hydroxylase 17/20-lyase expression in the baboon fetal adrenal
gland during the first half of gestation.
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