title: Selective alterations in insulin receptor substrates-1, -2 and -4 in theca but not granulosa cells from polycystic ovaries.
abstract: The elevated insulin concentrations that occur in many women with polycystic ovary syndrome (PCOS) can contribute significantly to ovarian hyperandrogenism. The objective of the present study was to compare the content of proximal insulin signalling molecules in theca and granulosa cells between polycystic ovaries and regular cycling controls. Individual follicles (3-7 mm) were obtained from 11 women with PCOS and 10 regularly cycling control women. The theca and granulosa cells were microdissected from each follicle. Total protein was extracted and signalling proteins were measured by western blot analysis. There was no difference in insulin receptor content between PCOS and controls in either theca or granulosa cells. Insulin receptor substrate (IRS)-1 and -2 were increased (P<0.05), but IRS-4 was decreased (P<0.03) in PCOS theca cells. There were no changes in IRS-1, -2 or -4 in granulosa cells. IRS-3 was undetectable in all samples. There were no changes in phosphatidyl inositol-3 kinase catalytic subunits p110alpha or p110beta in either theca or granulosa cells. These data demonstrate cell-specific alterations in IRS protein concentrations in theca cells from polycystic ovaries that are consistent with an exaggerated amplification of the insulin signal and which may play an important role in ovarian hyperandrogenism and thecal hyperplasia.
authors.affiliation: Department of Obstetrics and Gynecology, Cedars-Sinai Burns and Allen Research Institute, Cedars-Sinai Medical Center/The David Geffen School of Medicine at UCLA, 8700 Beverly Blvd., Davis 2066, Los Angeles, CA 90048, USA.
authors.forename: H-W
authors.initials: HW
authors.lastname: Yen
authors.forename: A J
authors.initials: AJ
authors.lastname: Jakimiuk
authors.forename: I
authors.initials: I
authors.lastname: Munir
authors.forename: D A
authors.initials: DA
authors.lastname: Magoffin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000818:Animals; D005260:Female; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013799:Theca Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C526292:IRS1 protein, human; C526297:IRS2 protein, human; C107686:IRS4 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D011972:Receptor, Insulin