Involvement of Inhibin-activin System in Follicular Growth Arrest in PCOS

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  • FUJIWARA,Toshihiro
    Department of Obstetrics and Gynecology, University of Tokyo Graduate School of Medicine

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  • (1)多嚢胞性卵巣症候群(PCOS)の卵胞発育障害におけるインヒビン・アクチビン系の関与(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」)

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Abstract

PCOS has several clinical features, of which is the ovulatory disorder. The pathophysiology of the follicular growth arrest has not been well elucidated. We focused on inhibin-activin-follistatin system, which are members of TGF-β growth and differentiation superfamily. Those substances were known to be synthesized and secreted in the ovarian follicle, being local regulators of the follicular growth. We found that there was optimal range in the amount of inhibin α mRNA to accomplish normal oocyte maturation and embryogenesis after fertilization. It was also shown that the amount of both inhibin A in the follicular fluid and inhibin α mRNA in the granulose cells increased in accordance with the follicle size. In addition the amount of inhibin A and B as well as inhibin α and βA mRNA significantly decreased in the PCOS follicles compared to those in normal cycling women of the same size. Furthermore it was suggested inhibin A had stimulatory effects on follicular development using mouse single follicle culture system. Taken together it can be concluded that inhibin plays an important role in the pathophysiology of the follicular growth arrest in PCOS. Another clinical issue is atypical endometrial hyperplasia (AEMH) or endometrial cancer (EC), which were caused by 'unopposed estrogen' condition of PCOS. We conducted conservative therapy to these diseases of the patients under forty years old who were eager to have children. In total 12 cases of AEMH and 17 cases of EC (stage Ia, G1) were recruited in the study. In AEMH cases 11 responded to the treatment and eight had conceived, of which five patients delivered. In EC cases 14 responded to the treatment and six had conceived, of which four patients delivered. Four case in AMEH and three cases in EC had relapsed. The precise analysis revealed that the mean of the endometrial thickness was larger in the pregnant group than in non-pregnant group. In addition it was also larger in pregnant cycle than in non-pregnant cycle within the pregnant group. This treatment seems to have clinical significance, though there is room to be improved in terms of the methods of both primary therapy and infertility treatment.

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