Cited by 51Growth Hormone and Insulin-like Growth FactorsHypothalamic control of reproductive hormonesRegulation of Appetite and Obesity

Butyrate increases intracellular calcium levels and enhances growth hormone release from rat anterior pituitary cells via the G-protein-coupled receptors GPR41 and 43

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Miletta, Maria Consolata, Petkovic, Vibor, Eblé, Andrée, Ammann, Roland A., Flück, Christa E., Mullis, Primus-E.·2014·PLoS ONE

Abstract

Butyrate is a short-chain fatty acid (SCFA) closely related to the ketone body ß-hydroxybutyrate (BHB), which is considered to be the major energy substrate during prolonged exercise or starvation. During fasting, serum growth hormone (GH) rises concomitantly with the accumulation of BHB and butyrate. Interactions between GH, ketone bodies and SCFA during the metabolic adaptation to fasting have been poorly investigated to date. In this study, we examined the effect of butyrate, an endogenous agonist for the two G-protein-coupled receptors (GPCR), GPR41 and 43, on non-stimulated and GH-releasing hormone (GHRH)-stimulated hGH secretion. Furthermore, we investigated the potential role of GPR41 and 43 on the generation of butyrate-induced intracellular Ca2+ signal and its ultimate impact on hGH secretion. To study this, wt-hGH was transfected into a rat pituitary tumour cell line stably expressing the human GHRH receptor. Treatment with butyrate promoted hGH synthesis and improved basal and GHRH-induced hGH-secretion. By acting through GPR41 and 43, butyrate enhanced intracellular free cytosolic Ca2+. Gene-specific silencing of these receptors led to a partial inhibition of the butyrate-induced intracellular Ca2+ rise resulting in a decrease of hGH secretion. This study suggests that butyrate is a metabolic intermediary, which contributes to the secretion and, therefore, to the metabolic actions of GH during fasting.

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  • Butyrate enhances growth hormone secretion in pituitary cells via GPR41/43 activation and intracellular accumulation of Ca2+.

    “Moreover, Miletta and colleagues found that butyrate enhances growth hormone (GH) secretion in pituitary cells via GPR41/43 activation and intracellular accumulation of Ca2+ (131).”

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Authors
Miletta, M. C., Petkovic, V., Eblé, A., Ammann, R. A., Flück, C. E., & Mullis, P.-E.
Affiliations
  • University Children’s Hospital Bern (CH)
  • University of Bern (CH)
Corresponding author
Mullis, Primus-E.
Venue
PLoS ONE
Published
2014-10-13
Volume
9
Issue
10
Pages
e107388
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2107519520
Cited by
51
References
46
Citations by year
2026: 7 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 8 · 2020: 6 · 2019: 4 · 2018: 3 · 2017: 3 · 2015: 3
FWCI
1.61
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • BORIS (University Library Bern) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Open Access CRIS of the University of Bern
Funders
  • National Science Foundation
  • Inselspital, Universitätsspital Bern
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (320000, 121998)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords
butyrate, short-chain fatty acids, growth hormone secretion, anterior pituitary cells, GPR41, GPR43, G protein-coupled receptors, intracellular calcium, growth hormone-releasing hormone, fasting, ketone bodies, beta-hydroxybutyrate, metabolic adaptation
MeSH terms
Animals, Calcium, Cell Line, Pituitary Gland, Anterior, Growth Hormone, Growth Hormone-Releasing Hormone, Butyric Acid, Gene Silencing, RNA, Small Interfering, Receptors, G-Protein-Coupled, Rats

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