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Effect of Acute Physiological Elevations of Insulin on Circulating Androgen Levels in Nonobese Women^*

MICHAEL P. DIAMOND, DAVID A. GRAINGER, ANDREA J. LAUDANO, KATHLEEN STARICK-ZYCH and RALPH A. DeFRONZO

Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Yale University School of Medicine (M.P.D., D.A.G., A.J.L., K.S.-Z.) New Haven, Connecticut 06510; and the Department of Medicine, University of Texas Health Science Center (R.A.D.) San Antonio, Texas 78284

Address requests for reprints to: Michael P. Diamond, M.D., Department of Obstetrics and Gynecology, Yale University School of Medicine, 333 Cedar Street, P.O. Box 3333, New Haven, Connecticut 06510.

Recipient of the Clinical Associate Physician Award from the NIH. Supported by Grant 186280 from the Juvenile Diabetes Foundation (to M.P.D.) and Grant RR-00125 from the General Clinical Research Center.

Current address: Center for Reproductive Medicine, Wichita, Kansas 67214.

Extreme pharmacological elevation of the circulating insulin level acutely lowers dehydroepiandrosterone sulfate (DHEAS) levels. To assess whether more physiological elevations in plasma insulin (due to exogenous infusion or endogenous secretion) would have similar effects, we examined the levels of DHEAS, androstenedione, testosterone, and free testosterone before and after euglycemic hyperinsulinemic and hyperglycemic hyperinsulinemic clamp studies. Studies were performed in women within 20% of ideal body weight after an overnight fast. Androgen levels were measured before and at the conclusion of studies in which either insulin was infused exogenously at 1 mU/kg·min or endogenous insulin secretion was stimulated for 2 h by elevation of the plasma glucose concentration by 125 mg/dL above basal levels by an exogenous glucose infusion. Basal plasma DHEAS (6.2 ± 0.5 µmol/L) declined to 5.2 ± 0.4 µmol/L (P < 0.001) during the euglycemic insulin clamp, without any significant change in testosterone, free testosterone, or androstenedione. During the hyperglycemic clamp, DHEAS fell from 6.7 ± 0.5 to 5.1 ± 0.4 µmol/h (P < 0.001) in response to endogenous hyperinsulinemia; plasma testosterone, free testosterone, and androstenedione did not change significantly. There was no correlation between the elevation in plasma insulin concentration and the fall in DHEAS during either the euglycemic or hyperglycemic clamps. However, the magnitude of fall of DHEAS was directly correlated with the initial DHEAS level in both the euglycemic (r = 0.51; P < 0.05) and hyperglycemic (r = 0.75; P < 0.01) studies. This association of hyperinsulinemia with a reduction of circulating levels of DHEAS, but not other C-19 steroids (e.g. testosterone and androstenedione) may reflect differential mechanisms by which DHEAS levels are regulated and suggests that insulin either inhibits its biosynthesis and/or secretion, or enhances its MCR. (J Clin Endocrinol Metab 72: 883–887, 1991)

^* Presented in part at the 19th Annual Meeting of the Society for Gynecologic Investigation, San Diego, CA, March 1989.

Received July 9, 1990.

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