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Adrenal Hyperandrogenism Is Induced by Fetal Androgen Excess in a Rhesus Monkey Model of Polycystic Ovary Syndrome

National Primate Research Center (R.Z., D.A.D., D.H.A.), Department of Obstetrics and Gynecology (I.M.B., D.H.A.), and Endocrinology-Reproductive Physiology Program (R.Z., I.M.B., D.H.A.), University of Wisconsin, Madison, Wisconsin 53715; and Reproductive Medicine and Infertility Associates (D.A.D.), Woodbury, Minnesota 55125

Address all correspondence and requests for reprints to: Rao Zhou, 3009 Da Vinci Drive, Westfield, Indiana 46074. E-mail: rzhou{at}wisc.edu.

Context: Adrenal androgen excess is found in approximately 25–60% of women with polycystic ovary syndrome (PCOS), but the mechanisms underlying PCOS-related adrenal androgen excess are unclear.

Objective: The objective of this study was to determine whether adrenal androgen excess is manifest in a nonhuman primate model for PCOS.

Participants: Six prenatally androgenized (PA) and six control female rhesus monkeys of similar age, body weight, and body mass index were studied during d 2–6 of two menstrual cycles or anovulatory 30-d periods.

Interventions: Predexamethasone adrenal steroid levels were assessed in the first cycle (cycle 1). In a subsequent cycle (cycle 2), occurring one to three cycles after cycle 1, adrenal steroids were determined 14.5–16.0 h after an im injection of 0.5 mg/kg dexamethasone (postdexamethasone levels) and after an iv injection of 50 µg ACTH-(1–39).

Results: Both before and after dexamethasone, serum levels of dehydroepiandrosterone (DHEA) in PA females exceeded those in controls. After ACTH injection, PA females exhibited higher circulating levels of DHEA, androstenedione, and corticosterone but comparable levels of 17-hydroxyprogesterone, cortisol, the sulfoconjugate of DHEA, and testosterone compared with controls.

Conclusion: Enhanced basal and ACTH-stimulated adrenal androgen levels in PA female monkeys may reflect up-regulation of 17,20 lyase activity in the adrenal zona reticularis, causing adrenal androgen excess comparable with that found in PCOS women with adrenal androgen excess. These findings open the possibility that PCOS adrenal hyperandrogenism may have its origins in fetal androgen excess reprogramming of adrenocortical function.

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