The Expression Of GDF-9 In PCOS And The Effects Of GDF9 On The Expression Of Emzyemes Involved In Hyperandrogenaemia

BackgroundPolycystic Ovary Syndrom (PCOS) is one of the most common causes of anovulation, infertility, and menstrual irregularities, affecting 5-10% of women of reproductive age worldwide. It has been defined as a syndrome involving Polycystic ovaries, hyperandrogenism, and anovulation with the exclusion of specific diseases of the ovaries, adrenals, and pituitary. This disorder is also a major risk factor for diabetes mellitus, hypertension, and cardiovascular disease. Therefore, PCOS is a significant issue for women beyond the reproductive endocrine abnormalities. Despite an enormous effort to define the cause of PCOS, the pathogenesis remain unclear, and there is no effective method to cure patients of PCOS. So understanding the mechanisms that cause PCOS is a major goal of medical research. Biochemical and clinical hyperandrogenism in PCOS, of ovarian and/or of adrenal origin, is evident in the majority of patients with PCOS (60-80%) women. Ovarian hyperandrogenism is mainly attributed to the defect of theca cells in PCOS. Increased luteinising hormone (LH) appear to amplify the intrinsic abnormality of theca steroidogenesis. The relatively decreased follicle-stimulating hormone (FSH) levels and intraovarian factors are also involved. GDF9 is one of the most important intraovarian factors. It has been revealed that the oocyte-secreted factors GDF-9 ( growth differentiation factor 9) is critical factors regulating follicular development and ovarian function. GDF-9 is involved in the formation of dominant follicle and oocyte maturation via regulating cellular differentiation, proliferation and function in autocrine and paracrine manners. In recent years,it has been found that GDF-9 inhibits 3' 5' -adenosine monophosphate-stimulated steroidogenesis in human granulosa cells. So we supposed that wheather GDF-9 play a key rol in the hyperandrogenaemia of PCOS.Objectives1 .To study the level of of GDF-9 in hunman follicular fluid obtained from women with PCOS and control.2.To study the transcription of StAR,P450scc,P450arom mRNA in hunman luteinized granulosa cell3.To revel the effects of GDF-9 on the expression of emzyemes involved in hyperandrogenaemia in PCOSMethods1.The level of GDF-9 protein in follicular fluid of PCOS groups( n=15 )and control groups (n=12) were measured by Western blotting.2. The level of transcription of StAR,P450scc,P450arom mRNA in luteinized granulosa cells of PCOS groups (n=15 ) and control groups (n=12) were measured by Realtime Quantitative PCR.3. Granulose cells obtained from PCOS women were cultured and GDF-9 was added. The transcription of StAR mRNA of luteinized granulosa cells were measured by Realtime Quantitative PCR.Results1 .The level of GDF-9 in follicular fluid were significantly lower in PCOS group than in control group (P<0.05).2.There were no significant differences in the expression of P450scc,P450arom between PCOS groups and control groups (P=0.24 and 0.21, respectively). However, the transcription of StAR mRNA were significantly higher in PCOS groups than control group (P=0.044).3.The transcription of StAR mRNA of hunman luteinized granulosa cells was significantly increased (P=0.017) when granulosa cells were treated with GDF-9(200ng/ml).ConclusionsReduced GDF-9 level in follicular fluid and increased expression of STAR in granulose cells of PCOS women as well as in vivo stimulation of GDF-9 on STAR expression were demonstrated, suggesting reduced GDF-9 may be not involved in the hyperandrogenaemia in PCOS by STAR.