(2)PCOSの排卵障害ならびにインスリン抵抗性に関する研究 : ラットモデルによる排卵障害,OHSSの研究とadiponectinからみたインスリン抵抗性の臨床研究(講演要旨,<特集>第58回シンポジウム2「PCOSの病態生理と臨床」)

概要

論文の詳細を見る
Although the criteria JSOG is a little bit different from Rotterdam criteria, 2 major symptoms such as hyperandrogenemia and insulin resistance attracts doctor's attention. In our study, we examined the effects of hyperandrogenemia on follicular development, ovulation process and follicular atresia. Animal model studies were performed concerning these effects which are shown below. Clinical studies are also shown below. We gave DHEA to immature female rats for 15 days following Lee's paper. We assessed the expressions of matrix metalloproteinase-2 (MMP-2) and lysyl oxidase in DHEA-treated rats. MMP-2 is well known to degrade the collagen of follicular walls. Lysyl oxidase is reported to crosslink collagen and elastin and to strengthen them. DHEA-treated rats have elevated all androgen such as testosterone, androstenedione and DHEAS, and actually have hyperandrogenemia. At day 15 MMP-2 activity was significantly reduced and lysyl oxidase mRNA was significantly increased in the ovaries of DHEA-treated rats compared to control rats. This date suspects that hyperandrogenemia might contribute to ovulation failure. DHEA treatment for 7 days caused an increase in the total number of follicules. However, DHEA treatment for 15 days increased the number of atretic follicles and caused the activation of Fas-FasLigand-Caspase-8. These results showed that apoptosis is one of the major mechanisms follicular atresia under hyperandrogenemia. We utilized Zucker (fa/fa) rats as an insulin resistance model. These rats have insulin resistance, but do not have DM. These rats have an increased total number of follicles and atretic follicles campared to control rats. Using Evans blue study, hyperstimulation treatment by PMSG-HCG following Ujioka's model caused an increase in vascular permeability to the ovary. These model rats have elevated expressions of VEGF, VEGFR-1 and VEGFR-2 in the ovaries compared to control rats. Continuing long treatment of GnRHagonist combined with hCG injection blocked the increase in vascular permeability and VEGF-VEGFR expressions. These results showed the possibility that prolonged treatment by GnRHagonist clinically may prevent the occurrence of OHSS. Moreover, OHSS treatment caused a decrease in claudin-5, tight junction protein, which seals endothelial cells. Therefore, vascular permeability was elevated in this situation. Prolonged GnRHa treatment blocked the decrease in claudin-5, and the increase in vascular permeability. Eighty percents of obese PCOS patients have insulin resistance. Forty percents of lean PCOS patients have insulin resistance. Almost all patients with insulin resistance have reduced serum adiponectin in obese PCOS. On the other hand, just 50% of patients with insulin resistance have reduces serum adionectin. Taken together, the pathophisiology of obese PCOS appears to be different from that of nonobese PCOS regarding to insulin resistance and serum adiponectin level.
社団法人日本産科婦人科学会の論文
2006-10-01

(2)PCOSの排卵障害ならびにインスリン抵抗性に関する研究 : ラットモデルによる排卵障害,OHSSの研究とadiponectinからみたインスリン抵抗性の臨床研究(講演要旨,<特集>第58回シンポジウム2「PCOSの病態生理と臨床」)

スポンサーリンク

概要

著者

関連論文

スポンサーリンク