Effect of hyperandrogenism on ovarian function

Abstract

The objective of the present work was to study the ovarian function when follicular development is induced during a hyperandrogenic condition. Female rats were injected either with chorionic gonadotropin (eCG group) to induce folliculogenesis or with eCG together with dehydroepiandrosterone to induce folliculogenesis in a hyperandrogenic condition (eCG+HA group). The control group was injected with vehicle. Ovarian mRNA levels of the PPARγ co-activator PGC1-α, the PPARγ co-repressor NCoR, and the main enzymes involved in the ovarian steroidogenesis (CYP17, 3β hydroxysteroid dehydrogenase (3β-HSD), 17β hydroxysteroid dehydrogenase (17β-HSD) CYP19A), and cyclooxygenase 2 (COX-2) were evaluated by real time polymerase chain reaction and protein expression of COX-2 was evaluated by Western Blotting. Ovarian steroidogenesis and both the oxidative and inflammatory status were also quantified. We found that eCG-induced folliculogenesis induced increased mRNA levels of PGC1-α and decreased those of NCoR as compared to controls. In addition, we found accumulation of estradiol and enhanced mRNA expression of CYP19A. A pro-inflammatory and a pro-oxidant status were also established. When folliculogenesis was induced in a hyperandrogenic condition, the mRNA levels of the PPARγ co-repressor NCoR remained higher than in controls and the pro-inflammatory and pro-oxidant status were enhanced. In addition, the enzymes involved in ovarian steroidogenesis were altered leading to the accumulation of testosterone and an unfavorable estradiol/testosterone ratio. These alterations led to abnormal follicular development.