Expression of insulin-receptor substrate-1 and-2 in ovaries from women with insulin resistance and from controls

Objective: To evaluate the role of insulin-receptor substrate (IRS)-1 and - 2 in ovary dysfunction in women with insulin resistance. Design: Immunoblotting and immunohistochemical analyses of the localization and staining intensity of IRS-1 and IRS-2 in the ovaries of women with the polycystic ovary syndrome (PCOS) and gestational diabetes mellitus. Setting: Department of Obstetrics and Gynecology, Turku University Central Hospital. Patient(s): Sections of ovary were obtained at the time of cesarean section from five volunteers without medical complications and three patients with gestational diabetes mellitus. Paraffin-embedded ovary sections were selec ted from those on file from the department of pathology; four were from wom en with a histologic diagnosis of PCOS and sec en were from women with endo metriosis (controls). Intervention(s): None. Main Outcome Measure(s): Protein expression of IRS in human ovary samples. Result(s): Immunoblotting with specific monoclonal and polyclonal antibodie s showed the presence of 165-kDa and 183-kDa proteins that corresponded to the size of IRS-1 and IRS-2, respectively, in normal pregnant ovaries and h uman cultured follicles. Immunohistochemical staining showed that positive IRS-2 expression in antral follicles was restricted to theca internal cells in ovulatory ovaries but was distributed widely in all compartments of fol licles in different stages in polycystic ovaries. Compared with follicles a t a similar stage of development in ovulatory ovaries, follicles in polycys tic ovaries showed decreased staining for IRS-1 in granulosa cells but incr eased staining for IRS-2 in theca internal cells. These features of IRS-1 a nd -2 expression were also noted in preantral and atretic follicles from pa tients with gestational diabetes mellitus compared with those who had uncom plicated pregnancy. Conclusion(s): This study highlights a shift of the follicular insulin sign al protein from IRS-1 to IRS-2 in insulin-resistant states and suggests an association between this change and ovarian abnormality in PCOS and gestati onal diabetes mellitus. (Fertil Steril(R) 2000;74:564-72. (C) 2000 by Ameri can Society for Reproductive Medicine.).