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Insulin Mediators Are the Signal Transduction System Responsible for Insulin’s Actions on Human Placental Steroidogenesis^*

Department of Medicine, Medical College of Virginia/Virginia Commonwealth University Richmond, Virginia 23298;
The Department of Pharmacology, University of Virginia Charlottesville, Virginia 22908

Address requests for reprints to: Dr. John E. Nestler, Division of Endocrinology and Metabolism, Medical College of Virginia, MCV Station, Box 111, Richmond, Virginia 23298β0111.

Abstract

To test the hypothesis that insulin mediators serve as the signal transduction system for insulin’s steroidogenic actions in human placental cytotrophoblasts, we examined the effects of two inositolglycan insulin mediators, the insulin pH 2.0 chiro-inositol mediator (IM-pH 2.0) and the insulin pH 1.3 myo-inositol mediator (IM-pH 1.3), on cytotrophoblastic steroidogenesis. When human cytotrophoblasts were incubated in medium supplemented with androstenedione for 24 h, treatment with IM-pH 2.0 or IM-pH 1.3 suppressed aromatase activity by 15% (P < 0.05) and 49% (P < 0.05), respectively, compared to insulin, which suppressed aromatase activity by 21% (P < 0.05). When cytotrophoblasts were incubated in medium supplemented with pregnenolone for 24 h, treatment with IM-pH 2.0 or IM-pH 1.3 stimulated 3β-hydroxysteroid dehydrogenase (3j8HSD) activity by 145% (P < 0.05) and 168% (P < 0.05), respectively, compared to insulin, which stimulated 3βHSD activity by 63% (P < 0.05). Suppression of aromatase activity and stimulation of 3βHSD activity by inositolglycan mediators were both concentration dependent. Moreover, preincubation of cytotrophoblasts with the antiinositolglycan antibody IGP completely abolished insulin’s ability to either inhibit aromatase or stimulate 3βHSD activity. These results indicate that insulin mediators mimic insulin’s effects on cytotrophoblastic aromatase and 3βHSD activities and suggest that inositolglycan mediators are the signal transduction mechanism responsible for insulin’s regulation of human placental steroid hormone biosynthesis. (Endocrinology 129: 2951β2956, 1991)

Footnotes

^* This work was supported by the Diabetes Research and Education Foundation, a research award from the Virginia Affiliate of the American Diabetes Association, and the Thomas F. and Kate Miller Jeffress Memorial Trust; other support was received from NIH Grant DK-14334 and Diabetes Endocrinology Research Center Grant NIH-DK-38942.

Received June 19, 1991.

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