PRELIMINARY EVIDENCE OF DIMINISHED STEROGENESIS DURING FOLLICULOGENESIS IN WOMEN WITH POLYCYSTIC OVARY SYNDROME

MOTTA AB; SANDER VA; HAPON MB; JAHN GA; LOMBARDI EP

San Francisco, California, USA

Congreso; ANDROGEN EXCESS & PCOS SOCIETY 6TH ANNUAL MEETING; 2008

ANDROGEN EXCESS & PCOS SOCIETY

PRELIMINARY EVIDENCE OF DIMINISHED STEROGENESIS DURING FOLLICULOGENESIS IN WOMEN WITH POLYCYSTIC OVARY SYNDROME Motta AB(1), Sander VA(1), Hapon MB(2), Jahn GA(2), Lombardi EP(3) (1)Laboratorio de Fisio-patología Ovárica, CEFYBO-UBA,CONICET-Buenos Aires, Argentina; (2)Laboratorio de Reproducción y Lactancia, IMBECU-CONICET, Mendoza, Argentina; and (3) Instituto de Ginecología y Reproducción (IFER), Buenos Aires, ArgentinaMultiple factors have been reported to regulate the environment of follicles from women with Polycystic Ovary Syndrome (PCOS). The aim of the present study was to investigate the intrinsic capacity of polycystic ovaries to respond to these factors. To this end, we evaluated the messenger RNAs (mRNAs) of the enzymes (StAR, P450 scc, P450 c17, 3 beta HSD) involved in the cascade of ovarian steroidogenesis (quantified by the production of progesterone and estradiol), the synthesis of prostaglandin E (PGE) and PGF2 alpha, and the abundance of cyclooxygenase 2 (COX2) in developing follicles. In addition, we determined the role of the transcriptional factors GATA-4 and GAT-6 (respectively related to the cellular differentiation and cellular proliferation) in the development of the dominant follicle. Patients with PCOS (n= 14) show increased circulating LH: FSH ratio but diminished steroidogenesis from early developing follicles as compared to controls (n=12) since progesterone and estradiol concentration from follicular fluid were diminished in PCOS patients when compared to controls. RT-PCR analysis confirmed that in PCOS patients mRNA abundance of both the P450scc enzyme and the transcriptional factor GATA-4 were diminished suggesting a poor cellular differentiation whereas the abundance of mRNA GATA-6 was increased in PCOS patients as compared to controls suggesting a high cellular proliferation. The enzymes P450 c17 and 3 beta HSD corresponding to PCOS patients show similar pattern than controls. In addition, the production of follicular prostaglandin F2 alpha (PGF 2 alpha) was diminished in PCOS patients as compared to controls.  We concluded that GATA transcriptional factors and prostanoids affect follicular steroidogenesis either directly or indirectly during follicular development. These abnormal balance of transcriptional factors leads to a diminished cellular differentiation of PCOS follicles and an increased cellular proliferation of these follicles which in turn leads to a deficient follicular steroidogenesis (supported in part by ANPCyT grants PICTR 32529 and PICT 949).