Effect Of Metformin On Serum Hormone And Overian Local Cell Factor Of Polycystic Ovary Syndrome Rats

Objective:Using the polycystic ovary syndrome(PCOS) rats model induced by letrozole as the study object,to investigate the relationship among insulin-like growth factor-I(IGF-I), transforming growth factor-betal(TGF-β1) and ovary pathology change in PCOS rats and to investigate the effects of metformin on PCOS rats and to analyse the possible mechanism.Methods:1. Establishment of PCOS animal modelForty female Wistar rats of six weeks age,with four days'regular estrus cycle,feeding for threedays to make them suit, were randomly divided into model group(30 cases) and control group(10 cases).The model group was administered letrozole at concentration of lmg/kg p.o.dissolved in 1%solution of carboxmethlycellulose(CMC) once daily,the treatment period was twenty-one days,while control group was fed normally.During this period,vaginal smears were collected daily for estrus cycle determonation. After completing the PCOS rats model,the model group rats were drawed ten randomly, according to vaginal smears results, serum hormone level and ovary tissue polycystic to assess model effect,when the success rates are over 80%,the model group remain rats were randomly divided into metformin treatment group(MF group) and placebo group(PCOS group),ten for each group.The MF group was administered metformin at concentration of 270mg/kg p.o.dissolved in distilled water,while PCOS group and control group was administered distilled water p.o., the treatment period was fourteen days.2. Histologic detection of ovariesThe ovary tissue of every group rats underwent paraffin imbedding, microtome section,HE staining and then observed their pathohistology by lighter microscope.3. Detection of the serum gonadal hormone and insulin levelThe level of serum luteinizing hormone(LH), follicle stimulating hormone(FSH), estradiol(E2), progesterone(P), testoterone(T) and insulin(INS) was detected by radioimmunoassay(RIA).4. Expression of IGF-I and TGF-β1 in the ovaryThe expression of IGF-I and TGF-β1 protein in every group ovary were detected and evaluated by immunohistochemistry and image analysis systerm.Results:1. Change of estrus cycles The estrus cycles of model group showed irregular change, which indicating the rats had no ovulation.2. Anatomical detection of ovariesThe everage ovary weight of PCOS group is higher than control group and MF group.Ovary surface is pale,has larger volume and is seen many the saccate expansion follicle.3. Histologic detection of ovariesIn PCOS group,it can be seen saccular dilatation follicle,the decreased number of corpora lutea,a thin layer of granulosa cells,the puff alignment granulosa cells and a thick layer of theca cells.In MF group,it can be seen increased granolar cell layer,decreased theca cell layer and inncreased corpora lutea.4. Detection of the serum gonadal hormone and insulin levelThe values of T,LH and INS in PCOS group are higher than those of the control group(P <0.05), The values of E2,FSH and P in PCOS group are lower than those of the control group(P <0.05). The values of T,LH and INS in MF group are lower than those of the PCOS group(P <0.05), The values of E2,FSH and P in MF group are higher than those of the PCOS group(P <0.05).5. Expression of IGF-I in the ovaryIGF-I expressed majorly in granolar cells and theca cells,not expressed in stromal cells. The expression of IGF-I in granular cells was significantly higher in PCOS group than in control group (P<0.05), The expression of IGF-I in granular cells was significantly lower in MF group than in PCOS group (P<0.05).6. Expression of TGF-β1 in the ovaryTGF-β1 expressed in occytes of primordial and preantral follicles,and lowly expressed in granolar cells, theca cells and stromal cells.There was no significant difference of expression in follicles occytes and granular cells. The expression of TGF-β1 in theca cells and stromal cells was significantly higher in PCOS group than in control group (P<0.05), The expression of TGF-P1 in theca cells and stromal cells was significantly lower in MF group than in PCOS group (P<0.05).Conclusions:1. Letrozole-induced model in rats can be served as the ideal model of PCOS,which has high dependability.2. The expression of IGF-I and TGF-β1 in the ovary is highly correlated with the pathogenesy of PCOS.