Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system.
To determine whether insulin stimulates human ovarian testosterone production in the polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system, thecal cells from polycystic ovary syndrome women were isolated and cultured. Insulin and insulin-like growth factor I stimulated thecal testosterone biosynthesis. Antibody blockade of the insulin receptor abolished insulin's stimulatory action, whereas effective antibody blockade of the insulin-like growth factor I receptor did not alter insulin's stimulation of thecal testosterone biosynthesis. A chiro-inositol containing glycan (INS-2) increased thecal testosterone biosynthesis. Preincubation of cells with an antiinositolglycan antibody (A23939 or alpha IGP) abolished insulin's stimulatory effect, but not that of hCG. These findings suggest that inositolglycans serve as the signal transduction system for insulin's stimulation of human thecal testosterone biosynthesis.
Nestler
J E
JE
Department of Internal Medicine, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298, USA. nestler@hsc.vcu.edu
Jakubowicz
D J
DJ
de Vargas
A F
AF
Brik
C
C
Quintero
N
N
Medina
F
F
D000328:Adult; D000906:Antibodies / Q000494:pharmacology; D005260:Female; D006801:Humans; D007294:Inositol / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D011134:Polysaccharides / Q000494:pharmacology; D011972:Receptor, Insulin / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction; D013739:Testosterone / Q000096:biosynthesis*; D013799:Theca Cells / Q000187:drug effects* / Q000378:metabolism*
D000906:Antibodies; D007328:Insulin; D011134:Polysaccharides; D013739:Testosterone; D007294:Inositol; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin