Abstract
β-hydroxybutyric acid (BHBA) regulates the synthesis and secretion of growth hormone (GH) and prolactin (PRL), but its mechanism is unknown. In this study, we detected the effects of BHBA on the activities of G protein signaling pathways, AMPK-α activity, GH, and PRL gene transcription, and GH and PRL secretion in dairy cow anterior pituitary cells (DCAPCs). The results showed that BHBA decreased intracellular cAMP levels and a subsequent reduction in protein kinase A (PKA) activity. Inhibition of PKA activity reduced cAMP response element-binding protein (CREB) phosphorylation, thereby inhibiting GH and PRL transcription and secretion. The effects of BHBA were attenuated by a specific Gαi inhibitor, pertussis toxin (PTX). In addition, intracellular BHBA uptake mediated by monocarboxylate transporter 1 (MCT1) could trigger AMPK signaling and result in the decrease in GH and PRL mRNA translation in DCAPCs cultured under low-glucose and non-glucose condition when compared with the high-glucose group. This study identifies a biochemical mechanism for the regulatory action of BHBA on GH and PRL gene transcription, translation, and secretion in DCAPCs, which may be one of the factors that regulate pituitary function during the transition period in dairy cows.
Highlights
Ketosis is a metabolic disorder that usually occurs in dairy cattle during the early lactation period when cows experience a state of negative energy balance and low blood glucose concentrations [1].This disorder is characterized by elevated concentrations of the ketone bodies β-hydroxybutyrate acid (BHBA), acetoacetate and acetone in blood, urine, and milk
The mRNA levels of growth hormone (GH) were markedly lower after the 24 h BHBA treatment (Figure 1A; p < 0.01), and the mRNA levels of PRL and pituitary-specific transcription factor-1 (Pit-1) were significantly lower after the 24 h BHBA treatment (Figure 1A; p < 0.05)
The mRNA levels of GH were markedly higher in the pertussis toxin (PTX) + BHBA group than in the BHBA treatment group (Figure 1C; p < 0.01), and the mRNA levels of PRL and Pit-1 were significantly higher in the PTX + BHBA group than in the BHBA treatment group (Figure 1C; p < 0.05)
Summary
Ketosis is a metabolic disorder that usually occurs in dairy cattle during the early lactation period when cows experience a state of negative energy balance and low blood glucose concentrations [1]. This disorder is characterized by elevated concentrations of the ketone bodies β-hydroxybutyrate acid (BHBA), acetoacetate and acetone in blood, urine, and milk. The secretion of growth hormone (GH) and prolactin (PRL) from the pituitary gland is modulated by various metabolic influences; in vivo experiments have revealed very large differences in the effect of BHBA on GH and PRL secretion depending on the physiological state of the animal. The effect and detailed mechanisms by which BHBA mediates bovine pituitary function remain to be elucidated through in vitro studies
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