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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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AMP-Activated Protein Kinases / metabolism
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Animals
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Cattle
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Cells, Cultured
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Cyclic AMP / metabolism
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Cyclic AMP Response Element-Binding Protein / metabolism
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Female
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Glucose / pharmacology
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Growth Hormone / antagonists & inhibitors
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Growth Hormone / genetics
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Growth Hormone / metabolism*
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Hydroxybutyrates / toxicity*
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Monocarboxylic Acid Transporters / genetics
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Monocarboxylic Acid Transporters / metabolism
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Pertussis Toxin / pharmacology
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Phosphorylation / drug effects
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Pituitary Gland, Anterior / cytology
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Pituitary Gland, Anterior / drug effects*
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Pituitary Gland, Anterior / metabolism
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Prolactin / antagonists & inhibitors
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Prolactin / metabolism*
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RNA, Messenger / metabolism
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Signal Transduction / drug effects*
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Symporters / genetics
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Symporters / metabolism
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Transcription Factor Pit-1 / genetics
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Transcription Factor Pit-1 / metabolism
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Transcription, Genetic / drug effects
Substances
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Cyclic AMP Response Element-Binding Protein
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Hydroxybutyrates
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Monocarboxylic Acid Transporters
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RNA, Messenger
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Symporters
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Transcription Factor Pit-1
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monocarboxylate transport protein 1
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Prolactin
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Growth Hormone
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Cyclic AMP
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Pertussis Toxin
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Cyclic AMP-Dependent Protein Kinases
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AMP-Activated Protein Kinases
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Glucose