Insulin mediators are the signal transduction system responsible for insulin's actions on human placental steroidogenesis.
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 less than 0.05) and 49% (P less than 0.05), respectively, compared to insulin, which suppressed aromatase activity by 21% (P less than 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 less than 0.05) and 168% (P less than 0.05), respectively, compared to insulin, which stimulated 3 beta HSD activity by 63% (P less than 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.
Nestler
J E
JE
Department of Medicine, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298.
Romero
G
G
Huang
L C
LC
Zhang
C G
CG
Larner
J
J
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000906:Antibodies; D047072:Aromatase Inhibitors; D005260:Female; D006801:Humans; D007294:Inositol / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011134:Polysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011247:Pregnancy; D015398:Signal Transduction; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism
D000906:Antibodies; D047072:Aromatase Inhibitors; D007328:Insulin; D011134:Polysaccharides; C068698:inositol-glycan; D007294:Inositol; D015096:3-Hydroxysteroid Dehydrogenases