Regulating Effects of 11-Deoxycorticosterone on 3beta-Hydroxysteroid Dehydrogenase

Abstract

Regulating Effects of 11-Deoxycorticosterone on 3 beta-Hydroxysteroid Dehydrogenase Progesterone plays a key role in ovulation and the formation of a corpus luteum, although its regulation remains poorly understood. The enzyme 3/J-hydroxysteroid dehydrogenase (3/iHSD) converts pregnenolone to progesterone and thus represents a critical step in progesterone biosynthesis. It has recently been discovered that the primate ovary synthesizes 11-deoxycorticosterone (DOC) in response to an ovulatory gonadotropin stimulus. Blockade of the mineralocorticoid receptor (MR), which serves as the receptor for DOC, prevents gonadotropin-induced progesterone synthesis. It is hypothesized that DOC augments the expression of 3/HSD following an ovulatory stimulus via MR-mediated mechanisms. The current studies were to determine if 3/iHSD is an MR target gene in H295R adrenocortical cells, which are used as a surrogate model of primate ovarian steroidogenesis. The results indicate that an increase in 3^HSD RNA is associated with the Forskolin treatment (receptor agonist), which was expected. The Forskolin treatment was statistically different from Forskolin+Flutamide (FL blocks androgen receptors), which suggests that 3/?HSD is regulated by androgen receptors and not mineralocorticoid receptors (such as the ones in DOC). The results also demonstrate that passage number affects steroidogenic properties of H295R cells.