Growth Hormone Alters Circulating Levels of Glycine and Hydroxyproline in Mice

Growth hormone (GH) has established effects on protein metabolism, such as increasing protein synthesis and decreasing amino acid degradation, but its effects on circulating amino acid levels are less studied. To investigate this relationship, metabolomic analyses were used to measure amino acid con...

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Main Authors: Jonathan A. Young, Silvana Duran-Ortiz, Stephen Bell, Kevin Funk, Yuan Tian, Qing Liu, Andrew D. Patterson, Edward O. List, Darlene E. Berryman, John J. Kopchick
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Metabolites
Subjects:
Online Access:https://www.mdpi.com/2218-1989/13/2/191
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author Jonathan A. Young
Silvana Duran-Ortiz
Stephen Bell
Kevin Funk
Yuan Tian
Qing Liu
Andrew D. Patterson
Edward O. List
Darlene E. Berryman
John J. Kopchick
author_facet Jonathan A. Young
Silvana Duran-Ortiz
Stephen Bell
Kevin Funk
Yuan Tian
Qing Liu
Andrew D. Patterson
Edward O. List
Darlene E. Berryman
John J. Kopchick
author_sort Jonathan A. Young
collection DOAJ
description Growth hormone (GH) has established effects on protein metabolism, such as increasing protein synthesis and decreasing amino acid degradation, but its effects on circulating amino acid levels are less studied. To investigate this relationship, metabolomic analyses were used to measure amino acid concentrations in plasma and feces of mice with alterations to the GH axis, namely bovine GH transgenic (bGH; increased GH action) and GH receptor knockout (GHRKO; GH resistant) mice. To determine the effects of acute GH treatment, GH-injected GH knockout (GHKO) mice were used to measure serum glycine. Furthermore, liver gene expression of glycine metabolism genes was assessed in bGH, GHRKO, and GH-injected GHKO mice. bGH mice had significantly decreased plasma glycine and increased hydroxyproline in both sexes, while GHRKO mice had increased plasma glycine in both sexes and decreased hydroxyproline in males. Glycine synthesis gene expression was decreased in bGH mice (Shmt1 in females and Shmt2 in males) and increased in GHRKO mice (Shmt2 in males). Acute GH treatment of GHKO mice caused decreased liver Shmt1 and Shmt2 expression and decreased serum glycine. In conclusion, GH alters circulating glycine and hydroxyproline levels in opposing directions, with the glycine changes at least partially driven by decreased glycine synthesis.
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spelling doaj.art-d6c1cf127a394246a0b5fc02261f21122023-11-16T22:04:10ZengMDPI AGMetabolites2218-19892023-01-0113219110.3390/metabo13020191Growth Hormone Alters Circulating Levels of Glycine and Hydroxyproline in MiceJonathan A. Young0Silvana Duran-Ortiz1Stephen Bell2Kevin Funk3Yuan Tian4Qing Liu5Andrew D. Patterson6Edward O. List7Darlene E. Berryman8John J. Kopchick9Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USAEdison Biotechnology Institute, Ohio University, Athens, OH 45701, USAHeritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USAEdison Biotechnology Institute, Ohio University, Athens, OH 45701, USADepartment of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, State College, PA 16803, USADepartment of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, State College, PA 16803, USADepartment of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, State College, PA 16803, USAEdison Biotechnology Institute, Ohio University, Athens, OH 45701, USAHeritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USAHeritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USAGrowth hormone (GH) has established effects on protein metabolism, such as increasing protein synthesis and decreasing amino acid degradation, but its effects on circulating amino acid levels are less studied. To investigate this relationship, metabolomic analyses were used to measure amino acid concentrations in plasma and feces of mice with alterations to the GH axis, namely bovine GH transgenic (bGH; increased GH action) and GH receptor knockout (GHRKO; GH resistant) mice. To determine the effects of acute GH treatment, GH-injected GH knockout (GHKO) mice were used to measure serum glycine. Furthermore, liver gene expression of glycine metabolism genes was assessed in bGH, GHRKO, and GH-injected GHKO mice. bGH mice had significantly decreased plasma glycine and increased hydroxyproline in both sexes, while GHRKO mice had increased plasma glycine in both sexes and decreased hydroxyproline in males. Glycine synthesis gene expression was decreased in bGH mice (Shmt1 in females and Shmt2 in males) and increased in GHRKO mice (Shmt2 in males). Acute GH treatment of GHKO mice caused decreased liver Shmt1 and Shmt2 expression and decreased serum glycine. In conclusion, GH alters circulating glycine and hydroxyproline levels in opposing directions, with the glycine changes at least partially driven by decreased glycine synthesis.https://www.mdpi.com/2218-1989/13/2/191growth hormonemetabolomicsamino acidstranscriptomics
spellingShingle Jonathan A. Young
Silvana Duran-Ortiz
Stephen Bell
Kevin Funk
Yuan Tian
Qing Liu
Andrew D. Patterson
Edward O. List
Darlene E. Berryman
John J. Kopchick
Growth Hormone Alters Circulating Levels of Glycine and Hydroxyproline in Mice
Metabolites
growth hormone
metabolomics
amino acids
transcriptomics
title Growth Hormone Alters Circulating Levels of Glycine and Hydroxyproline in Mice
title_full Growth Hormone Alters Circulating Levels of Glycine and Hydroxyproline in Mice
title_fullStr Growth Hormone Alters Circulating Levels of Glycine and Hydroxyproline in Mice
title_full_unstemmed Growth Hormone Alters Circulating Levels of Glycine and Hydroxyproline in Mice
title_short Growth Hormone Alters Circulating Levels of Glycine and Hydroxyproline in Mice
title_sort growth hormone alters circulating levels of glycine and hydroxyproline in mice
topic growth hormone
metabolomics
amino acids
transcriptomics
url https://www.mdpi.com/2218-1989/13/2/191
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