Fetal programming of adrenal androgen excess

Lessons from a nonhuman primate model of polycystic ovary syndrome

D. Abbott, R. Zhou, I. Bird, D. Dumesic, Alan J Conley

Research output: Contribution to journalArticle

47 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)145-158
Number of pages14
JournalEndocrine Development
Volume13
DOIs
StatePublished - 2008

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Polycystic Ovary Syndrome
Fetal Development
Primates
Androgens
pioglitazone
Haplorhini
17-alpha-Hydroxyprogesterone
Dehydroepiandrosterone Sulfate
Macaca mulatta
Adrenocorticotropic Hormone
Dehydroepiandrosterone
Insulin
Serum
Zona Reticularis
Zona Fasciculata
Steroid 17-alpha-Hydroxylase
Androstenedione
Adrenal Cortex
Corticosterone
Glucocorticoids

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Pediatrics, Perinatology, and Child Health
  • Endocrinology
  • Endocrine and Autonomic Systems

Cite this

Fetal programming of adrenal androgen excess : Lessons from a nonhuman primate model of polycystic ovary syndrome. / Abbott, D.; Zhou, R.; Bird, I.; Dumesic, D.; Conley, Alan J.

In: Endocrine Development, Vol. 13, 2008, p. 145-158.

Research output: Contribution to journalArticle

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