Action Of Platelet-Derived-Growth Factor And Epidermal Growth Factors In Pathogenesis Of Polycystic Ovarian Syndrome

Polycystic ovarian syndrome (PCOS), mainly featuring the androgen excess and the chronic anovulation, is one of the most common endocrine disorder diseases among the women of childbearing ages. The incidency rate of it accounts for 5%-21% among the infertility women and 75%-80% among the anovulatory women. In 1935, Stein and Leventhal initially reported a group of syndrome principally characterizing amenorrhea, obesity, hirsutism, anovulation and the bilateral ovarian polycystic changes. Due to the very extensive changes of physiopathology which involves in genetics, neuroendocrinology, glycometabolism, adipic-metabolism, protein-metabolism and the abnormality of partial regulating and controlling factors of ovary, its research is still remained one of the hotspots in Gynecological endocrinology field by now.PCOS mainly characterizes androgen excess along with chronic anovulatory. Hypersecretion of androgen in ovary is the key reason to result in the PCOS. It is crucial to understand the androgen excess —the characteristics changes in ovary, for elucidate polycystic ovary syndrome pathogenesis. In previous reports, it has been suggested that PCOS is likely to be a result of the cytokines regulator disorder. Platelet-derived-growth factor (PDGF) is a strong mitogen. It was identified in platelets, macrophages, vascular endothelioid cells, vascular smooth muscle cells, placenta and embryo cells, mesenchymal cells and altered SV40 et al. PDGF play a dominant role in regulated ovum growth and embryonic development, whose biological actions is mediated through two receptor tyrosine kinases. Epidermal growth factor (EGF) is an alone polypeptide chains which is constituted of 53 amino acid residues, it is secreted by mandibular gland , pancreas, thyroid gland, liver, oocyte, embryoblast et al; EGF regulated ovaries function through the way of paracrine in ovarian granulosa cells, oviducts and uterus, for example, the proliferation and differentiationof cells and steroidogenesis. EGF might regulate the aromatase activity in granulosa cells and associated with PCOS.The human luteinic granulosa cells in ovaries were cultured in vitro.To investigate aromatization and the mechanism of action of platelet-derived-growth factor and epidermal growth factor on oestradiol biosynthesis in human ovarian granulosa cells from polycystic ovary syndrome.Prior to testing for aromatase activity, the cells were pre-incubated for the difference times, in the presence of testosterone as substrate, with or without PDGF, EGF. Meantime, the concentration of PDGF and EGF in the serum and follicular fluid were measured in order to elucidate the hyperandrogenic pathogenesis of PCOS.Material and Methods1. All subjects were derived into two group: ?PCOS group (n=16), BMI wasl9-23.5 ( 21.15 ± 2.36 ) kg/m2 according to the diagnostic standard(OBSTETRICS AND GYNECOLOGY, the sixth edit). ?The normal control group(n=20), BMI 18.51-23 (20.31 ±1.63) kg/m2, women whose menstrual regularity ,the normal ovulation and endocrine function, and have normal ovary by Vagina Ultrasonic evaluated but Fallopian tube blocked or male infertility.All patients were of without other complications of Obstetrics and Gynecology .All women were received the same induced ovulation drugs before the follicular centesis within 3 months.2. After oocyte adoptedCDthe peripheral blood were extracted and the follicular aspirates were centrifuged and adopted supernatant to measure the quantity of PDGF and EGF in two fluids. ?Granulosa cells were prepared from follicular aspirates, and pre-incubated for 0h,48h,120h.The test period was for 3h in the presence of testosterone (10"7 M) as substrate, with or without PDGF (lOng/ml) and/or EGF (lOng/ml). At the end of the culture, the medium was collected for the measurements of oestradiol by RIA, the cells were lysed with 50uI 0.1M sodium hydroxide and their protein concentration were assayed by CBBG-250/BSA in order to correct E2.Results1. There are no significant difference between PCOS group and the normal group in mean ages, BMI (p >0.05).2. The serum concentration of PDGF and EGF in PCOS group and normal group was no significant difference (p >0.05).3. The follicular fluid concentrations of PDGF and EGF in PCOS group wassignificant higher than those of the normal group (p<0.05).4. The serum concentrations of PDGF and EGF in normal group were significant higher than those of the follicular fluid (p<0.05).5. The serum concentrations of PDGF and EGF in PCOS group were significant higher than those of the follicular fluid (p<0.05).6. Granulosa cells were cultured for Oh, 48h, 120h in PCOS group, the addition of PDGF to the cultures for 3h induced a significant (p<0.05) increase in oestradiol production than those of normal group.7. Granulosa cells were cultured for Oh, 48h, 120h in PCOS group, the addition of EGF to the cultures for 3h induced a significant (p<0.05) difference in oestradiol production than those of normal group.8. Granulosa cells were cultured for Oh, 120h in PCOS group, the addition of PDGF and EGF to the cultures for 3h induced a significant (p<0.Q5) increase in oestradiol production than those of normal group; but none significent difference for 48h(p >0.05).Statistical analysisThe data was calculated using mean+SD. Comparisons between different groups of patients was undertaken using Student'paired /-test or /'test. SPSS 11.5 was used for both studies. There was a statistical significance when^<0.05.Conclusions1. The PDGF and EGF secreted abnormity in PCOS group, PDGF and EGF were likely associated with the occured of PCOS.2. Experiment in vitro:?PDGF stimulated the androgen transforming estradiol in granulose cells of ovaries from PCOS patients.?EGF suppressed the androgen transforming estradiol in granulose cells of ovaries fromPCOS patients.3. The regulated action of PDGF and EGF on aromatase activity in granulosa cells of ovaries were contradiction. The action sites of PDGF and EGF might be the same one.