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Disorders of the Human Adrenal Cortex

Editor(s): Flück C.E. (Bern) 
Miller W.L. (San Francisco, Calif.) 
Cover
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Fetal Programming of Adrenal Androgen Excess: Lessons from a Nonhuman Primate Model of Polycystic Ovary Syndrome

Abbott D.a-c · Zhou R.a · Bird I.a,c · Dumesic D.b,d · Conley A.e

Author affiliations

aDepartment of Obstetrics and Gynecology, b Wisconsin National Primate Research Center and c Endocrinology-Reproductive Physiology Training Program, University of Wisconsin, Madison, Wisc., d Reproductive Medicine and Infertility Associates, Woodbury, Minn., and ePopulation Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, Calif., USA

Related Articles for ""

Flück CE, Miller WL (eds): Disorders of the Human Adrenal Cortex. Endocr Dev. Basel, Karger, 2008, vol 13, pp 145-158

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Abstract

Adrenal androgen excess is found in adult female rhesus monkeys previously exposed to androgen treatment during early gestation. In adulthood, such prenatally androgenized female monkeys exhibit elevated basal circulating levels of dehydroepiandrosterone sulfate (DHEAS), typical of polycystic ovary syndrome (PCOS) women with adrenal androgen excess. Further androgen and glucocorticoid abnormalities in PA female monkeys are revealed by acute ACTH stimulation: DHEA, androstenedione and corticosterone responses are all elevated compared to responses in controls. Pioglitazone treatment, however, diminishes circulating DHEAS responses to ACTH in both prenatally androgenized and control female monkeys, while increasing the 17-hydroxyprogesterone response and reducing the DHEA to 17-hydroxyprogesterone ratio. Since 60-min post-ACTH serum values for 17-hydroxyprogesterone correlate negatively with basal serum insulin levels (all female monkeys on pioglitazone and placebo treatment combined), while similar DHEAS values correlate positively with basal serum insulin levels, circulating insulin levels may preferentially support adrenal androgen biosynthesis in both prenatally androgenized and control female rhesus monkeys. Overall, our findings suggest that differentiation of the monkey adrenal cortex in a hyperandrogenic fetal environment may permanently upregulate adult adrenal androgen biosynthesis through specific elevation of 17,20-lyase activity in the zona fasciculata-reticularis. As adult prenatally androgenized female rhesus monkeys closely emulate PCOS-like symptoms, excess fetal androgen programming may contribute to adult adrenal androgen excess in women with PCOS.


Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: May 20, 2008
Cover Date: 2008

Number of Print Pages: 14
Number of Figures: 0
Number of Tables: 0

ISBN: 978-3-8055-8580-4 (Print)
eISBN: 978-3-8055-8581-1 (Online)


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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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