Progesterone stimulates cortisol production in the maturing bovine cumulus-oocyte complex

Abstract

In the bovine cumulus oophorus, 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1)-mediated cortisol production dramatically increases during the periovulatory period. This event is closely associated with increased progesterone (P4) production, implying a functional connection between these C21 steroids. In this study, we investigated the mutual regulation of P4 and cortisol production in the bovine cumulus oophorus. Bovine cumulus-oocyte complexes (COCs) were aspirated from follicles 2-5 mm in diameter and subjected to in vitro maturation (IVM) for 24 h in an M199 supplemented with fetal calf serum (FCS) and follicle-stimulating hormone (FSH). COCs were treated with trilostane (0, 0.1, 1, 10 mM), an inhibitor of P4 synthesis, RU486 (0, 0.1, 1, 10 mM), a receptor antagonist for the progesterone receptor (PR) and glucocorticoid receptor (GR), and various concentrations of a synthetic progestogen nomegestrol acetate (NA; 0, 0.001, 0.01, 0.1, 1, 10 mM) to examine effect of P4. The effects of cortisol (0, 0.1, 1, 10 mM) were also examined in the presence or absence of trilostane. Trilostane and RU486 suppressed cumulus expansion, cortisol production, and HSD11B1 but not hexose-6-phosphate dehydrogenase (H6PDH) expression. Concomitant treatment with NA reversed the effects of trilostane. Unlike NA, cortisol did not alter the antagonistic effects of trilostane on cumulus expansion and HSD11B1 expression. Cortisol did not affect P4 production or steroidogenic acute regulatory protein (STAR), cholesterol side-chain cleavage enzyme (CYP11A1), 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1), and HSD11B1 expression. Collectively, these results indicate that locally produced P4 is crucial in regulating the local glucocorticoid environment through PRtg in the maturing bovine cumulus oophorus. Cortisol, however, does not appear to regulate P4 or its production.

Keywords: Cortisol; Cumulus cells; HSD11B1; IVM; Progesterone.