Elevated IGF-1 induced female rats perpetuates the PCOS phenotype : Pathological mechanism of IGF-1 in polycystic ovary syndrome.

OBJECTIVES: This study was designated to establish a PCOS rat model with recombinant human insulin growth factor-1 (RH-IGF-1). We made assessment on the characteristics of hyperinsulinemia and hyperandrogenism in the rat model.

DESIGN: This study performed the characteristics of PCOS upon RH-IGF-1inejction and evaluated the disease process of PCOS syndrome caused by the insulin resistant pathological condition of IGF-1 based on the comparative study of in vivo test.

SETTING: The experiment was conducted in the experimental research center of Yinzhou NO.2 hospital, Ningbo, Zhejiang Province, China.

MATERIALS AND METHODS: Thirty-four female Sprague-Dawley (SD) immature rats aged 21 days, were randomly divided rats divided into two groups. Those treated with recombinant human insulin growth factor-1(RH-IGF-1) 2mg/100g daily were in RH-IGF-1 group(n=20), and those with 0.9% Sodium Chloride 0.2ml/100g daily were in the saline group (n =14). The experiment was carried out in two stages. In Stage I, rats were anesthetized upon the first estrous cycle in the saline group with tissue and blood samples collected(n=7), and rats in the RH-IGF-1 treated group were anesthetized on the 5th day after vaginal opening (VO) (n=10). In Stage II, rats in the saline group were anesthetized after three complete cycles (n=7), meanwhile, while on the 15th day after VO (n=10) for those in the RH-IGF-1 group.

RESULTS: We have found that compared with the control group, rats injected with RH-IGF-1 expressed an early vaginal opening, disordered estrous cycle, polycystic ovaries and significantly increased ovarian weight/body weight ratio. And from the perspective of hormone secretion, their androgen increased significantly and the insulin resistance index also elevated distinctly, possessing main characteristics similar to PCOS.

LIMITATIONS: In this study, we were limited by the inability to examine IGF-1 in hypothalamus. IGF-1 in hypothalamus and in vitro experiments would be taken into consideration for further study in the future.

CONCLUSIONS: These findings suggest that IGF-1 may be a key factor in the pathogenesis of PCOS, and the increase of androgen may be the pathological result, not the cause of polycystic ovary syndrome.