Luteoprotective roles of luteinizing hormone are mediated by not only progesterone production but also glucocorticoid conversion in bovine corpus luteum

Abstract

Luteinizing hormone (LH) is known as a key regulator of corpus luteum (CL) function, but the luteoprotective mechanisms of LH in the maintenance of bovine CL function are not well understood. The current study investigated if LH increases cell viability and induces cortisol conversion, and if the luteoprotective action of LH is mediated by stimulating the local production and action of progesterone (P4) and/or cortisol. Cultured bovine luteal cells obtained at the mid-luteal stage (Days 8-12 of the estrous cycle) were treated for 24 hr with LH (10 ng/ml) with/without onapristone (OP, a specific P4 receptor antagonist; 100 µM), cortisone (1 µM), and aminoglutethimide (AGT, a specific inhibitor of cytochrome P450 side-chain cleavage; 100 µM). LH with and without OP significantly increased the mRNA and protein expressions of 11β-hydroxysteroid dehydrogenase (HSD11B) 1, but did not affect the mRNA or protein expression of HSD11B2. These treatments also significantly increased HSD11B1 activity. Cell viability was significantly increased by LH alone or by LH in combination with cortisone and OP. LH in combination with OP or AGT significantly decreased cell viability as compared to LH alone. The overall results suggest that LH stimulates not only P4 production but also HSD11B1 expression, thereby increasing the cortisol concentration in the bovine CL, and that LH prevents cell death through these survival pathways. LH may consequently support CL function during the luteal phase in cattle.

The Janus Face of Stress on Reproduction: From Health to Disease

“…A possible mechanism of the enhanced pregnancy rate can be the apoptosis inhibiting effect of GCs on luteal cells, as the maintained luteal function contributes to the survival of the fetus [ 68 ].…”

Localization patterns of steroid and luteinizing hormone receptors in the corpus luteum of Nelore (Bos taurus indicus) cows throughout the estrous cycle

“…The mechanism involved in reentry of luteal cells in cell cycle/apoptosis triggered by PGF is related to proapoptotic cytokines gene expression (IL8, IL1B, TNF and FASL; Atli et al, 2012;Miyamoto et al, 2010). Since intraluteal P4 and cortisol (Kawaguchi et al, 2013) are dependent on LH, and suppress FAS and Caspase-3 mRNA expression (Komiyama et al, 2008;Okuda et al, 2004) the drop of LHR observed at the end of luteal phase in our study may be the key role in luteolysis process.…”

The effects of luteinizing hormone as a suppression factor for apoptosis in bovine luteal cells in vitro

“…This study investigates the anti‐apoptotic role of LH during the mid‐luteal phase and its mechanism via intracellular signalling. Previous study showed protective effects of LH against apoptosis via P4 and cortisol production (Kawaguchi et al., 2013). While the role of PKC and cAMP in this matter has been predicted (Tatsukawa et al., 2006), the direct connection between LH, intracellular signalling, P4, as well as cell viability has not been elucidated.…”