The Research On Relationship Between Leptin Postreceptor Signal Transduction Molecular STAT3 Phosphorylation In Ovarain Luteinizated Granulosa Cells And Mechanism Of Polycystic Ovarian Syndrome

Objective: About 50% polycystic ovarian syndrome (PCOS) patients are obese, and after symptoms of PCOS appear, weight still intends to increase and cause reproduction endocrine disturbance. Leptin can directly repress the effect of IGF-I on ovary granulosa cells, and restrains cell differentiation and ovum maturate, at last causes anovulation. However, the machanism of action is still unkown. JAK/STAT pathway is the main path of leptin signal transduction, this way is stimulated by leptin long receptor. This research detected the levels of leptin long receptor mRNA (OB-RLmRNA) and intracellular signal transduction molecular p-STAT3 in ovary of obese and nonobese PCOS patients, through which to analyze the effect of leptin on machanism of PCOS morbility, especially obese PCOS patients. Leptin may aggravate the reproduction endocrine disturbance of PCOS patients. Meanwhile, we cultured ovary granulosa cells in vitro and stimulated by human leptin with different concentrations, observed the two index, OB-RLmRNA and p-STAT3. Assess the relationship amony the two index, leptin and PCOS, whether leptin can affect the obese PCOS morbility. We also presume the leptin concentration which can cause leptin resistance in granulosa cells and judge whether there is leptin resistance in ovary of obese PCOS patient.Methods: Chose 10 obese PCOS patients (obese PCOS group), 10 nonobese PCOS patients (nonobese PCOS group), 10 obese normal patients (obese group) and 10 nonobese normal patients undergoing IVF-ET as control group. Granulosa cells were extracted from each patient and divided into two part, one was used to detected the level of OB-RLmRNA with RT-PCR and another was intracellular signal transduction molecular p-STAT3 with Western blot. Meanwhile we extracted granulosa cells from 10 normal patients ovaries and cultured them in vitro, then stimulated by human leptin with different concentrations (0, 10, 100, 1000 ng/ml). Respectively the levels of OB-RLmRNA and p-STAT3 were detected with RT-PCR and Western blot in granulosa cells stimulated by different concentrations leptin. Results: (1) The levels of OB-RLmRNA of each group were different, and compared with each other, the differences had statistical significance (p<0.05), the OB-RLmRNA level of obese PCOS group was the highest, and then was obese normal group, nonobese PCOS group and control group. (2) The level of p-STAT3 of obese PCOS group , obese normal group, nonobese PCOS group and control group was repectively (24.28±0.51), (21.31±1.32), (11.69±0.67), (9.03±0.20). Compared with each group, the differences had statistical significance (p<0.05). (3) Leptin can stimulate the expressions of OB-RLmRNA and p-STAT3 in granulosa cells cultured in vitro (p<0.05). The levels of these two index depended on the leptin concentration. When leptin concentration was 100ng/ml, the levels reached the peak, then began to decrease.Conclusion: (1) in PCOS women, the levels of serum leptin increase and imrove the expressions of OB-RLmRNA and p-STAT3 in granulosa cells. the reaction of granulosa cells to leptin is in accentuation; leptin may be involved in phsiopathology of obese PCOS and cause anovulation. (2) JAK2/STAT3 signal transduction pathway may be involved in the effect of leptin on anovulation of PCOS.