Adrenal hyperandrogenism is induced by fetal androgen excess in a rhesus monkey model of polycystic ovary syndrome.
BACKGROUND
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.


METHODS
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.


METHODS
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 i.m. injection of 0.5 mg/kg dexamethasone (postdexamethasone levels) and after an i.v. injection of 50 microg 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 17alpha-hydroxyprogesterone, cortisol, the sulfoconjugate of DHEA, and testosterone compared with controls.


CONCLUSIONS
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.
Zhou
Rao
R
National Primate Research Center, University of Wisconsin, Madison 53715, USA. rzhou@wisc.edu
Bird
Ian M
IM
Dumesic
Daniel A
DA
Abbott
David H
DH
D000311:Adrenal Glands / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D019540:Area Under Curve; D003687:Dehydroepiandrosterone / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006728:Hormones / Q000097:blood; D017588:Hyperandrogenism / Q000209:etiology* / Q000378:metabolism*; D008253:Macaca mulatta; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013256:Steroids / Q000097:blood
D000728:Androgens; D006728:Hormones; D013256:Steroids; D003687:Dehydroepiandrosterone; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone