OBJECTIVE: To assess insulin and insulin-like growth factor I (IGF-I) action in women with polycystic ovarian syndrome (PCOS). DESIGN: Hyperinsulinemia was determined by measuring the insulin responses during a 2-hour oral glucose tolerance test (OGTT). Quantification of in vivo insulin action was determined by a frequently sampled intravenous (IV) OGTT with minimal modeling analysis. In vitro sensitivity to insulin at physiological and supraphysiological concentrations and to IGF-I was assessed by examining colony formation of two hematopoietic cell populations, burst-forming units of the erythroid line (BFU-E) and human leukemia virus immortalized T-cell lines. (The proliferative responses of BFU-E, a primary tissue explant, are presumably conditioned by factors in the immediate blood-borne environment, whereas proliferative responses of T-cell lines are presumed to reflect intrinsic target-cell hormone sensitivity.) SETTING: Tertiary care research institution. PATIENTS: Eight patients (4 obese and 4 nonobese) with PCOS and three healthy women for reference controls. RESULTS: Nonobese (P less than 0.04) and obese patients with PCOS (P less than 0.01) both demonstrated significant hyperinsulinemia after OGTT. In vivo insulin resistance was observed in both nonobese (P less than 0.03) and obese PCOS subjects (P less than 0.01) using frequently sampled IV OGTT. Both nonobese (P less than 0.03) and obese patients with PCOS (P less than 0.01) had blunted in vitro clonal responses of BFU-E, with normal T-cell line clonal responsiveness to physiological levels of insulin and normal BFU-E and T-cell line clonal responses to IGF-I. CONCLUSIONS: These findings demonstrate the following in both nonobese and obese patients with PCOS: (1) there is in vivo hyperinsulinemia and resistance to insulin action on glucose disposal; (2) with BFU-E, there is in vitro resistance to the mitogenic action of insulin but normal responsiveness to IGF-I; and (3) there is normal in vitro mitogenic responsiveness of T-cell lines to both insulin and IGF-I. The intrinsically normal mitogenic responsiveness to insulin and, especially to IGF-I, whether or not under the influence of the bloodborne milieu, provides a mechanism whereby hyperinsulinemia could directly contribute to the ovarian abnormalities that characterize PCOS.
OBJECTIVE: To assess insulin and insulin-like growth factor I (IGF-I) action in women with polycystic ovarian syndrome (PCOS). DESIGN:Hyperinsulinemia was determined by measuring the insulin responses during a 2-hour oral glucose tolerance test (OGTT). Quantification of in vivo insulin action was determined by a frequently sampled intravenous (IV) OGTT with minimal modeling analysis. In vitro sensitivity to insulin at physiological and supraphysiological concentrations and to IGF-I was assessed by examining colony formation of two hematopoietic cell populations, burst-forming units of the erythroid line (BFU-E) and humanleukemia virus immortalized T-cell lines. (The proliferative responses of BFU-E, a primary tissue explant, are presumably conditioned by factors in the immediate blood-borne environment, whereas proliferative responses of T-cell lines are presumed to reflect intrinsic target-cell hormone sensitivity.) SETTING: Tertiary care research institution. PATIENTS: Eight patients (4 obese and 4 nonobese) with PCOS and three healthy women for reference controls. RESULTS: Nonobese (P less than 0.04) and obesepatients with PCOS (P less than 0.01) both demonstrated significant hyperinsulinemia after OGTT. In vivo insulin resistance was observed in both nonobese (P less than 0.03) and obese PCOS subjects (P less than 0.01) using frequently sampled IV OGTT. Both nonobese (P less than 0.03) and obesepatients with PCOS (P less than 0.01) had blunted in vitro clonal responses of BFU-E, with normal T-cell line clonal responsiveness to physiological levels of insulin and normal BFU-E and T-cell line clonal responses to IGF-I. CONCLUSIONS: These findings demonstrate the following in both nonobese and obesepatients with PCOS: (1) there is in vivo hyperinsulinemia and resistance to insulin action on glucose disposal; (2) with BFU-E, there is in vitro resistance to the mitogenic action of insulin but normal responsiveness to IGF-I; and (3) there is normal in vitro mitogenic responsiveness of T-cell lines to both insulin and IGF-I. The intrinsically normal mitogenic responsiveness to insulin and, especially to IGF-I, whether or not under the influence of the bloodborne milieu, provides a mechanism whereby hyperinsulinemia could directly contribute to the ovarian abnormalities that characterize PCOS.