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Functional Capacity of Fetal Zone Cells of the Baboon Fetal Adrenal Gland: A Major Source of -Inhibin¹

^a Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23507 ^b Department of Obstetrics/Gynecology, McGill University Faculty of Medicine, Montreal, Canada H3A 1A1 ^c Departments of Obstetrics/Gynecology/Reproductive Sciences and Physiology, The Center for Studies in Reproduction, The University of Maryland School of Medicine, Baltimore, Maryland 21201

We have shown that ACTH receptor mRNA expression and steroidogenesis were increased in the transitional zone and decreased in the fetal zone of the baboon fetal adrenal in the second half of gestation. Thus, we proposed that there is a divergence in ACTH receptor-mediated zone-specific steroidogenesis within the fetal adrenal during mid to late gestation. We have also demonstrated that fetal serum -inhibin levels decline with advancing development. It is possible, therefore, that the subunit of inhibin provides a good marker of fetal zone cellular function and that the changes in circulating fetal -inhibin with advancing pregnancy reflect ontogenetic changes in fetal adrenal cortical zone-specific cell function. However, it remains to be determined whether the fetal adrenal is a major source of circulating -inhibin in the fetus and whether -inhibin is expressed in the fetal, definitive, and/or transitional zones. Therefore, the current study compared fetal serum -inhibin levels with immunocytochemical localization of -inhibin in baboon fetal adrenals obtained on Days 60 (early), 100 (mid), and 165 or 182 (late) of gestation (term averages Day 184) from animals untreated or treated with betamethasone, which we previously demonstrated suppressed fetal pituitary ACTH and adrenal weight. Fetal serum -inhibin levels (mean ± SE) were greater (p < 0.05) at mid (5863 ± 730 µl eq/ml) than at late (3246 ± 379) gestation and were reduced (p < 0.05) by betamethasone. The inhibin subunit was expressed in abundant quantities in the fetal adrenal cortex, but not in medulla, throughout gestation. At mid and late gestation, -inhibin was expressed throughout the fetal adrenal cortex but most intensely in the innermost area of fetal zone cells. By late gestation, the fetal adrenal exhibited a gradient of -inhibin expression. Thus, the outermost definitive zone cells were devoid of -inhibin, the transitional zone exhibited a relatively low -inhibin content, and fetal zone cells continued to exhibit extensive expression of -inhibin. Betamethasone diminished the intensity of -inhibin expression throughout the fetal adrenal cortex. These results indicate that the fetal adrenal fetal zone is a significant source of circulating -inhibin in the baboon fetus and that -inhibin provides a good marker to study the developmental regulation of fetal zone-specific adrenocortical function.

¹ This work was supported by NIH Research Grant R01 HD-13294 and the Frazier Endowment Fund of the Royal Victoria Hospital, Montreal.

² Correspondence: Gerald J. Pepe, Department of Physiological Sciences, Eastern Virginia Medical School, P.O. Box 1980, Norfolk, VA 23501–1980. FAX: 757 624 2269; gjp{at}borg.evms.edu

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