Implication of cortisol and 11β-hydroxysteroid dehydrogenase enzymes in the development of porcine (Sus scrofa domestica) ovarian follicles and cysts

Abstract

This study investigated cortisol inactivation by 11β-hydroxysteroid dehydrogenase (11β HSD) enzymes in porcine granulosa cells from antral follicles at different developmental stages and in ovarian cysts. In granulosa cells, cortisol oxidation increased threefold with antral follicle diameter (P< 0.001). This trend was paralleled by a threefold increase in NADP⁺-dependent 11β-dehydrogenase activity in granulosa cell homogenates with follicle diameter. Intact granulosa cells from ovarian cysts exhibited significantly lower enzyme activities than cells from large antral follicles. Neither intact cells norcell homogenates displayed net 11-ketosteroid reductase activities. Since porcine follicular fluid (FF) from large antral follicles and ovarian cysts contains hydrophobic inhibitors of glucocorticoid metabolism by type 1 11β HSD, this studyalso investigated whether levels of 11β HSD inhibitors changed during follicle growth and could affect cortisol metabolism in granulosa cells. The extent of inhibition of 11β HSD1 activity in rat kidney homogenates decreased progressively from 50 ± 8% inhibition by FF from small antral follicles (P< 0.001) to 23 ± 6% by large antral FF (P< 0.05). Cyst fluid inhibited 11β HSD1 activity by 59 ± 4% (P< 0.001). Likewise, net cortisol oxidation in granulosa cells was significantly decreased by large antral FF (35–48% inhibition,P< 0.05) and cyst fluid (45–75% inhibition,P< 0.01). We conclude that inactivation of cortisol by 11β HSD enzymes in porcine granulosa cells increases with follicle development but is significantly decreased in ovarian cysts. Moreover, changes in ovarian cortisol metabolism are accompanied by corresponding changes in the levels of paracrine inhibitors of 11β HSD1 within growing ovarian follicles and cysts, implicating cortisol in follicle growth and cyst development.