INSULIN MEDIATORS ARE THE SIGNAL TRANSDUCTION SYSTEM RESPONSIBLE FOR INSULINS ACTIONS ON HUMAN PLACENTAL STEROIDOGENESIS

To test the hypothesis that insulin mediators serve as the 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 3-beta-hydroxysteroid dehydrogenase (3-beta-HSD) activity by 145% (P < 0.05) and 168% (P < 0.05), respectively, compared to insulin, which stimulated 3-beta-HSD activity by 63% (P < 0.05). Suppression of aromatase activity and stimulation of 3-beta-HSD activity by inositolglycan mediators were both concentration dependent. Moreover, preincubation of cytotrophoblasts with the antiinositolglycan antibody alpha-IGP completely abolished insulin's ability to either inhibit aromatase or stimulate 3-beta-HSD activity. These results indicate that insulin mediators mimic insulin's effects on cytotrophoblastic aromatase and 3-beta-HSD activities and suggest that inositolglycan mediators are the signal transduction mechanism responsible for insulin's regulation of human placental steroid hormone biosynthesis.