Mice with an RGS-insensitive Gαi2 protein show growth hormone axis dysfunction

S Thierry Omouessi; Jeffrey R Leipprandt; Marie-Yvonne Akoume; Raelene Charbeneau; Susan Wade; Richard R Neubig

doi:10.1016/j.mce.2020.111098

Mice with an RGS-insensitive Gα_i2 protein show growth hormone axis dysfunction

Mol Cell Endocrinol. 2021 Feb 5:521:111098. doi: 10.1016/j.mce.2020.111098. Epub 2020 Dec 2.

Authors

S Thierry Omouessi¹, Jeffrey R Leipprandt², Marie-Yvonne Akoume³, Raelene Charbeneau⁴, Susan Wade⁴, Richard R Neubig⁵

Affiliations

¹ Department of Pharmacology, University of Michigan Medical School, Michigan, USA; Department of Physiology, Faculty of Medicine, Université des Sciences de la Santé (USS) de Libreville, Libreville, Gabon. Electronic address: omouessi@hotmail.fr.
² Department of Pharmacology and Toxicology, Michigan State University, Michigan, USA.
³ International Research Institute of Biomedical Sciences & Biotechnology-Carles Kambangoye (IRBK), Université Internationale de Libreville, Essassa, Gabon; Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Sainte-Justine University Hospital Research Center, Montréal, Quebec, Canada.
⁴ Department of Pharmacology, University of Michigan Medical School, Michigan, USA.
⁵ Department of Pharmacology, University of Michigan Medical School, Michigan, USA; Department of Pharmacology and Toxicology, Michigan State University, Michigan, USA.

PMID: 33278490
DOI: 10.1016/j.mce.2020.111098

Abstract

Mice carrying an RGS-insensitive Gαi2 mutation display growth retardation early after birth. Although the growth hormone (GH)-axis is a key endocrine modulator of postnatal growth, its functional state in these mice has not been characterized. The present study was undertaken to address this issue. Results revealed that pituitary mRNA levels for GH, prolactin (PRL), somatostatin (SST), GH-releasing-hormone receptor (GHRH-R) and GH secretagogue receptor (GHS-R) were decreased in mutants compared to controls. These changes were reflected by a significant decrease in plasma levels of GH, IGF-1 and IGF-binding protein-3 (IGFBP-3). Mutants were also less responsive to GHRH and ghrelin (GhL) on GH stimulation of release from pituitary primary cell cultures. In contrast, they were more sensitive to the inhibitory effect of SST. These data provide the first evidence for an alteration of the functional state of the GH-axis in Gαi2G184S mice that likely contributes to their growth retardation.

Keywords: GHRH; Growth hormone; IGF-1; Pituitary; RGS proteins; Somatostatin.

MeSH terms

Animals
Cells, Cultured
Female
GTP-Binding Protein alpha Subunit, Gi2 / genetics*
GTP-Binding Protein alpha Subunit, Gi2 / metabolism
Ghrelin / pharmacology
Growth Disorders / genetics*
Growth Disorders / metabolism*
Growth Hormone / blood
Growth Hormone / genetics
Growth Hormone / metabolism
Growth Hormone-Releasing Hormone / blood
Growth Hormone-Releasing Hormone / genetics
Growth Hormone-Releasing Hormone / pharmacology
Insulin-Like Growth Factor Binding Protein 3 / blood
Insulin-Like Growth Factor Binding Protein 3 / genetics
Insulin-Like Growth Factor I / genetics
Insulin-Like Growth Factor I / metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mutation
Pituitary Gland / drug effects
Pituitary Gland / metabolism
Prolactin / genetics
Prolactin / metabolism
RGS Proteins / genetics
RGS Proteins / metabolism*
Real-Time Polymerase Chain Reaction
Receptors, Ghrelin / metabolism
Receptors, Neuropeptide / genetics
Receptors, Neuropeptide / metabolism
Receptors, Pituitary Hormone-Regulating Hormone / genetics
Receptors, Pituitary Hormone-Regulating Hormone / metabolism
Signal Transduction / drug effects
Signal Transduction / genetics*
Somatostatin / genetics
Somatostatin / metabolism
Somatostatin / pharmacology

Substances

Ghrelin
Insulin-Like Growth Factor Binding Protein 3
RGS Proteins
Receptors, Ghrelin
Receptors, Neuropeptide
Receptors, Pituitary Hormone-Regulating Hormone
somatocrinin receptor
Somatostatin
Insulin-Like Growth Factor I
Prolactin
Growth Hormone
Growth Hormone-Releasing Hormone
GTP-Binding Protein alpha Subunit, Gi2
somatotropin releasing hormone receptor