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Timing of Prenatal Androgen Excess Determines Differential Impairment in Insulin Secretion and Action in Adult Female Rhesus Monkeys¹

Wisconsin Regional Primate Research Center (J.R.E., D.A.D., J.W.K., D.H.A.), Department of Obstetrics and Gynecology (J.R.E., D.H.A.), Endocrinology-Reproductive Physiology Program (J.R.E., D.H.A.), and Department of Physiology (J.W.K.), University of Wisconsin, Madison, Wisconsin 53715-1299; and Department of Obstetrics and Gynecology, Mayo Clinic (D.A.D.), Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Prof. David H. Abbott, Department of Obstetrics and Gynecology, Wisconsin Regional Primate Research Center, University of Wisconsin, 1220 Capitol Court, Madison, Wisconsin 53715. E-mail: abbott{at}primate.wisc.edu

This study determined whether timing of prenatal androgen excess resulted in differential impairment of insulin-glucose homeostasis in adult female rhesus monkeys. Ten female rhesus monkeys exposed to testosterone propionate starting on gestational day 40 (early treated), 9 females exposed to testosterone propionate starting between gestational days 100–115 (late treated), and 15 control females were studied. The modified minimal model was used to examine various measures derived from an iv glucose tolerance test, with regression analysis performed between these variables and body mass index. In addition, the disposition index (DI) and the hyperbolic relationship between insulin sensitivity (S_I) and acute insulin response to glucose were examined. Early treated females demonstrated impaired pancreatic ß-cell function, as shown by diminished DI and decreased percentile ranking for the hyperbolic relationship between S_I and acute insulin response to glucose. In contrast, late treated females exhibited both an increase in DI and a negative relationship between body mass index and S_I. These results suggest that prenatal androgen excess in female rhesus monkeys, regardless of gestational timing, perturbs insulin-glucose homeodynamics, with androgen excess in early and late gestation impairing pancreatic ß-cell function and altering insulin sensitivity, respectively.

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