Substantial further advances in our understanding of adrenal development, steroid biosynthesis and adrenocortical disorders necessitate another look at this small but complex organ. In this volume, leaders in the fields of adrenal development, biochemistry and genetics review the most recent findings from bench and bedside research. New aspects of adrenal development and zonation and the novel ‘backdoor’ pathway to androgen synthesis are discussed. P450 oxidoreductase deficiency (a newly described form of congenital adrenal hyperplasia) and long-term outcome of prenatal treatment of 21-hydroxylase deficiency are examined. An update on ACTH resistance and adrenal Cushing’s syndrome is provided. Finally, the role of adrenal steroidogenesis in arterial hypertension and fetal programming of adrenal androgen excess as a possible explanation for polycystic ovary syndrome in later life are analyzed. This book will be of great interest to pediatric, adult and reproductive endocrinologists, clinical geneticists, developmental biologists and basic scientists working in the fields of endocrinology and steroidogenesis.
145 - 158: Fetal Programming of Adrenal Androgen Excess: Lessons from a Nonhuman Primate Model of Polycystic Ovary Syndrome Free
-
Published:2008
-
Book Series: Endocrine DevelopmentSubject Area: Endocrinology , Further Areas , Genetics , Pathology and Cell Biology , Women's and Children's Health
David H. Abbott, Rao Zhou, Ian M. Bird, Daniel A. Dumesic, Alan J. Conley, 2008. "Fetal Programming of Adrenal Androgen Excess: Lessons from a Nonhuman Primate Model of Polycystic Ovary Syndrome", Disorders of the Human Adrenal Cortex, C.E. Flück, W.L. Miller
Download citation file:
Abstract
Adrenal androgen excess is found in adult female rhesus monkeys previously exposed to androgen treatmentduring early gestation. In adulthood, such prenatally androgenized female monkeys exhibit elevatedbasal circulating levels of dehydroepiandrosterone sulfate (DHEAS), typical of polycystic ovary syndrome(PCOS) women with adrenal androgen excess. Further androgen and glucocorticoid abnormalities in PAfemale monkeys are revealed by acute ACTH stimulation: DHEA, androstenedione and corticosteroneresponses are all elevated compared to responses in controls. Pioglitazone treatment, however, diminishescirculating DHEAS responses to ACTH in both prenatally androgenized and control female monkeys, whileincreasing 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 seruminsulin levels (all female monkeys on pioglitazone and placebo treatment combined), while similar DHEASvalues correlate positively with basal serum insulin levels, circulating insulin levels may preferentially supportadrenal 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 fetalenvironment may permanently upregulate adult adrenal androgen biosynthesis through specific elevationof 17,20-lyase activity in the zona fasciculata-reticularis. As adult prenatally androgenized female rhesusmonkeys closely emulate PCOS-like symptoms, excess fetal androgen programming may contribute toadult adrenal androgen excess in women with PCOS.
