title: Butyrate increases intracellular calcium levels and enhances growth hormone release from rat anterior pituitary cells via the G-protein-coupled receptors GPR41 and 43.
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.
authors.affiliation: Division of Paediatric Endocrinology, Diabetology and Metabolism and Department of Clinical Research, University Children's Hospital, Bern, Switzerland.
authors.forename: Maria Consolata
authors.initials: MC
authors.lastname: Miletta
authors.affiliation: Division of Paediatric Endocrinology, Diabetology and Metabolism and Department of Clinical Research, University Children's Hospital, Bern, Switzerland.
authors.forename: Vibor
authors.initials: V
authors.lastname: Petkovic
authors.affiliation: Division of Paediatric Endocrinology, Diabetology and Metabolism and Department of Clinical Research, University Children's Hospital, Bern, Switzerland.
authors.forename: Andrée
authors.initials: A
authors.lastname: Eblé
authors.affiliation: Department of Paediatrics, University of Bern, Bern, Switzerland.
authors.forename: Roland A
authors.initials: RA
authors.lastname: Ammann
authors.affiliation: Division of Paediatric Endocrinology, Diabetology and Metabolism and Department of Clinical Research, University Children's Hospital, Bern, Switzerland.
authors.forename: Christa E
authors.initials: CE
authors.lastname: Flück
authors.affiliation: Division of Paediatric Endocrinology, Diabetology and Metabolism and Department of Clinical Research, University Children's Hospital, Bern, Switzerland.
authors.forename: Primus-E
authors.initials: PE
authors.lastname: Mullis
mesh_terms: D000818:Animals; D020148:Butyric Acid / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D020868:Gene Silencing; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D034741:RNA, Small Interfering; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
chemical_list: C518630:Ffar2 protein, rat; C520305:Gper1 protein, rat; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D020148:Butyric Acid; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D002118:Calcium