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A Nguyen, Department of Population Health and Reproduction, University of California at Davis, Davis, United States
S Mapes, Department of Population Health and Reproduction, University of California at Davis, Davis, United States
C Corbin, Department of Population Health and Reproduction, University of California at Davis, Davis, United States
A Conley, Department of Population Health and Reproduction, University of California at Davis, Davis, United States

Correspondence: Aj Conley, Email: ajconley{at}ucdavis.edu

Abstract

Human adrenarche is associated with the establishment of a functional zona reticularis (ZR) and increasing secretion of dehydroepiandrosterone (DHEA) in sulphated form (DS). Rhesus macaques are not believed to undergo adrenarche, though they clearly establish a functional ZR after birth. However, the origins of the rhesus ZR are not well defined. Therefore, we investigated the zonal development, steroidogenic enzyme expression and morphology of rhesus adrenals from 1 day to 14 months of age. Immuno-histochemistry was conducted to determine expression profiles of the steroidogenic enzymes 17alpha-hydroxylase/17,20-lyase cytochrome P450 (P450c17), 21-hydroxylase cytochrome P450 (P450c21), 3beta-hydroxysteroid dehydrogenase/delta5-4 isomerase (3beta-HSD), the redox partner NADPH-cytochrome P450 oxidoreductase (CPR), as well as the accessory protein cytochrome b5 (b5), a marker of the primate ZR. The rhesus ZR is mature by 3 months of age based on differentiation of the innermost zone which lacks 3beta-HSD, but exhibits increased b5 expression during this period. Further, the ZR develops in neonates from a previously described dense band of cells which we show expresses b5, P450c17, CPR, and P450c21 throughout maturation. The fetal zone (FZ) is distinguished from the ZR by its lack of P450c21, and ZR development proceeded as the FZ regressed with two important implications: neither FZ regression nor ZR maturation can be monitored independently by circulating adrenal androgens, and these events must be induced by different factors in rhesus, and likely humans. Collectively, these data demonstrate that ZR development begins before birth in the rhesus, proceeding concomitant with FZ regression post-natally, suggesting that rhesus experiences morphological adrenarche during the first three months of life.

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