β-Hydroxybutyric Acid Inhibits Growth Hormone-Releasing Hormone Synthesis and Secretion Through the GPR109A/Extracellular Signal-Regulated 1/2 Signalling Pathway in the Hypothalamus

β‐hydroxybutyric acid (BHBA) has recently been shown to regulate hormone synthesis and secretion in the hypothalamus. However, little is known about the effects of BHBA‐mediated hormone regulation or the detailed mechanisms by which BHBA regulates growth hormone‐releasing hormone (GHRH) synthesis an...

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Bibliographic Details
Published in:Journal of neuroendocrinology 2015-03, Vol.27 (3), p.212-222
Main Authors: Fu, S.-P., Liu, B.-R., Wang, J.-F., Xue, W.-J., Liu, H.-M., Zeng, Y.-L., Huang, B.-X., Li, S.-N., Lv, Q.-K., Wang, W., Liu, J.-X.
Format: Article
Language:English
Subjects:
3-Hydroxybutyric Acid - antagonists & inhibitors
3-Hydroxybutyric Acid - cerebrospinal fluid
3-Hydroxybutyric Acid - pharmacology
3-Hydroxybutyric Acid - physiology
Animals
Butadienes - pharmacology
Cells, Cultured
ERK1/2
Extracellular Signal-Regulated MAP Kinases - metabolism
Female
GPR109A
growth hormone-releasing hormone
Growth Hormone-Releasing Hormone - biosynthesis
Growth Hormone-Releasing Hormone - secretion
Homeodomain Proteins - biosynthesis
Humans
hypothalamus
Hypothalamus - metabolism
Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors
Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors
Nitriles - pharmacology
Pertussis Toxin - pharmacology
Primary Cell Culture
Rats
Receptors, G-Protein-Coupled - biosynthesis
Receptors, Nicotinic - biosynthesis
Signal Transduction - drug effects
β-hydroxybutyric acid
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Summary:β‐hydroxybutyric acid (BHBA) has recently been shown to regulate hormone synthesis and secretion in the hypothalamus. However, little is known about the effects of BHBA‐mediated hormone regulation or the detailed mechanisms by which BHBA regulates growth hormone‐releasing hormone (GHRH) synthesis and secretion. In the present study, we examined the expression of the BHBA receptor GPR109A in primary hypothalamic cell cultures. We hypothesised that BHBA regulates GHRH via GPR109A and its downstream signals. Initial in vivo studies conducted in rats demonstrated that GHRH mRNA expression in the hypothalamus was strongly inversely correlated with BHBA levels in the cerebrospinal fluid during postnatal development (r = −0.89, P 
ISSN:0953-8194
1365-2826
DOI:10.1111/jne.12256