The Relationship Between The Expression Of P-STAT3 And SOCS3 In Granulosa Cells And Leptin Level In Patients With PCOS

BackgroundPolycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and affects all the life of those women. Recent prevalance studies have suggested that 5-10% of premenopauseal women have the full syndrome of hyperandrogenism, hyperinsulinemia, insulin resistance, disorder secretion of Gn, hirsum, obesity, chronic anovulation, and polycystic ovaries. It may lead to complications such as disturbance in menstrution, hirsutism, obesity, infertility, cardiovascular diseases, diabetes mellitus, carcinoma of endometrium and other diseases. It hurts women's mental and physical health. But, the causes of the disease remain not well known. Some investigators regarded that PCOS may be related to abnormal release of GnRH, hyperandrogenism, hyperinsulinemia and insulin resistance. The discovery of leptin, and its association with energy balance and the reproductive endocrine axis, has led to considerable investigations of the relationship between PCOS, characterized by both obesity and reproductive abnormalities, and leptin synthesis. Recently, leptin resistance had been regarded involved in the pathogenesis and clinical chatacteristic of PCOS.Leptin is the product of the obese gene. Leptin is mainly produced in white adipose tissue although expression has also been demonstrated in the fundus of thestomach and in skeletal muscle. Leptin has many biological effects. It is important in regulating energy metabolism and adipose tissue mass. As a metabolism hormone, leptin can regulate the secretion of insulin, glucidic and lipidic metabolism. Recently, it has been found that leptin is associated with reproduction. It can regulate the secretion of GnRH and LH, pregnancy and lactation. In ob/ob mice, which do not have circulating leptin, treatment with recombinant leptin not only reduces the mice's body weight gradulatelly, but also increases their ovarian and uterine weights and restores fertility.The classical investigation suggests that leptin is a link between fat tissue and reproductive system.Leptin was therefore initially considered a miracle drug for treatment of obesity. However, obese people often have elevated leptin levels and leptin administration showed only very limited effects. Recent data have indicated that this is likely due to desensitization for the leptin signal, a phenomenon now often referred to as leptin resistance.Leptin resistance may be situated at four distinct levels: the disorder of the proportion of leptin and its binding protein in blood, saturable transport of leptin across the blood-brain barrier, abnormalities at the level of leptin receptor and abnormalities at the level of post-receptor signal transduction. The last one is the focus of investigations.JAK-STAT (Janus protein tyrosine Kinase, JAK; signal transducer and activator of transcription, STAT) signaling pathway is regarded the main one of letpin signaling. Leptin receptor belongs to the class I cytokine receptor family. Like all other class I cytokine receptors, leptin receptor lacks any intrinsic kinase activity, and uses cytoplasmic-associated kinases of the JAK family. Leptin binding results in formation of a receptor complex leading to cross-phosphorylation and activation of the JAKs.These activated JAKs then rapidly phosphorylate tyrosine residues in thecytosolic domain of the receptor. Such phosphorylated residues provide binding sites for signaling molecules including members of the STAT family. STATs themselves are also subject to JAK-mediated phosphorylation, inducing their homo- or heterodimerization, their release from the receptor complex, and subsequent translocation to the nucleus, where they can modulate transcription of specific target genes. SOCS (Suppressor of cytokine signaling) system is regarded as the main postreceptor inhibitors of leptin action. Any disfunction or disorder of the J AK-STAT pathway or SOCS system may leads to leptin resistance. Impaired phosphorylation of STATs was found in obesity people and rodent animals while excess pression of SOCS3 was regarded as th...