scholarly journals Growth hormone regulation of metabolic gene expression in muscle: a microarray study in hypopituitary men

2007 ◽  
Vol 293 (1) ◽  
pp. E364-E371 ◽  
Author(s):  
Klara Sjögren ◽  
Kin-Chuen Leung ◽  
Warren Kaplan ◽  
Margaret Gardiner-Garden ◽  
James Gibney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Hormone ◽  
Lipid Oxidation ◽  
Expression Profiles ◽  
Whole Body ◽  
Circadian Gene ◽  
Gh Treatment ◽  
Substrate Metabolism ◽  
Igf I

Muscle is a target of growth hormone (GH) action and a major contributor to whole body metabolism. Little is known about how GH regulates metabolic processes in muscle or the extent to which muscle contributes to changes in whole body substrate metabolism during GH treatment. To identify GH-responsive genes that regulate substrate metabolism in muscle, we studied six hypopituitary men who underwent whole body metabolic measurement and skeletal muscle biopsies before and after 2 wk of GH treatment (0.5 mg/day). Transcript profiles of four subjects were analyzed using Affymetrix GeneChips. Serum insulin-like growth factor I (IGF-I) and procollagens I and III were measured by RIA. GH increased serum IGF-I and procollagens I and III, enhanced whole body lipid oxidation, reduced carbohydrate oxidation, and stimulated protein synthesis. It induced gene expression of IGF-I and collagens in muscle. GH reduced expression of several enzymes regulating lipid oxidation and energy production. It reduced calpain 3, increased ribosomal protein L38 expression, and displayed mixed effects on genes encoding myofibrillar proteins. It increased expression of circadian gene CLOCK, and reduced that of PERIOD. In summary, GH exerted concordant effects on muscle expression and blood levels of IGF-I and collagens. It induced changes in genes regulating protein metabolism in parallel with a whole body anabolic effect. The discordance between muscle gene expression profiles and metabolic responses suggests that muscle is unlikely to contribute to GH-induced stimulation of whole body energy and lipid metabolism. GH may regulate circadian function in skeletal muscle by modulating circadian gene expression with possible metabolic consequences.

scholarly journals Exogenous growth hormone induces somatotrophic gene expression in neonatal liver and skeletal muscle

2000 ◽  
Vol 278 (4) ◽  
pp. R838-R844 ◽  
Author(s):  
A. J. Lewis ◽  
T. J. Wester ◽  
D. G. Burrin ◽  
M. J. Dauncey
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Hormone ◽  
Intracellular Signaling ◽  
Posttranscriptional Regulation ◽  
Plasma Concentrations ◽  
Gh Treatment ◽  
Rnase Protection ◽  
Neonatal Pigs ◽  
Igf I

The extent to which the local somatotrophic axis is functional in extrahepatic tissues in the neonate is unclear. We therefore determined the expression of growth hormone (GH) receptor (GHR), and insulin-like growth factors I and II (IGF-I and IGF-II) mRNA in liver and skeletal muscle (longissimus) of neonatal pigs given daily intramuscular injections of either recombinant porcine GH (1 mg/kg body wt; n = 6) or saline ( n = 5) for 7 days. Exogenous GH increased plasma concentrations of GH 30-fold and IGF-I threefold. Abundances of specific mRNA in liver and muscle were measured by RNase protection assays (values are arbitrary density units). In liver, GH treatment increased GHR (6.0 vs. 9.7; P< 0.01) and IGF-I (5.2 vs. 49.0; P < 0.001) but not IGF-II (19.5 vs. 17.2) mRNA. In muscle, GH treatment increased IGF-I mRNA (13.3 vs. 22.8; P < 0.05) but not GHR (8.3 vs. 9.5) or IGF-II (16.1 vs. 16.9). These results demonstrate that exogenous GH can induce local somatotrophic function predominantly in liver but also in muscle of newborn pigs. Our novel finding on the selective increase in muscle IGF-I but not GHR gene expression suggests differences in posttranscriptional regulation and/or intracellular signaling mechanisms.

scholarly journals Dairy cows experience selective reduction of the hepatic growth hormone receptor during the periparturient period

2004 ◽  
Vol 181 (2) ◽  
pp. 281-290 ◽  
Author(s):  
J Wook Kim ◽  
RP Rhoads ◽  
SS Block ◽  
TR Overton ◽  
SJ Frank ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Hormone ◽  
Dairy Cows ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Late Pregnancy ◽  
Target Tissue ◽  
Ghr Gene ◽  
Igf I

At parturition, dairy cows experience a 70% reduction in plasma IGF-I. This reduction coincides with decreased abundance of GHR1A, the liver-specific transcript of the growth hormone receptor (GHR) gene, suggesting impaired growth hormone-dependent synthesis of IGF-I. It is not immediately obvious that the periparturient reduction in GHR1A is sufficient to reduce hepatic GHR abundance. This is because approximately 50% of total GHR mRNA abundance in prepartum liver is accounted for by ubiquitously expressed transcripts which remain collectively unchanged at parturition. In addition, the possibility that parturition alters GHR expression in other growth hormone target tissue has not been examined. To address these questions, we measured GHR gene expression and GHR protein in liver and skeletal muscle of four dairy cows on days -35,+3 and+56 (relative to parturition on day 0). Hepatic GHR abundance and GHR1A transcripts were lower on day+3 than on day -35 and returned to late pregnancy value by day+56. Additional studies in two other groups of cows indicated that the hepatic levels of the GHR protein recovered substantially within 10 days after parturition. These changes occurred without variation in the abundance of HNF4, a liver-enriched transcription factor activating the promoter responsible for GHR1A synthesis. In contrast to liver, levels of GHR gene expression and GHR protein were identical on days -35,+3 and+56 in skeletal muscle. These data suggest a role for the GHR in regulating tissue-specific changes in growth hormone responsiveness in periparturient dairy cows.

scholarly journals FNDC5 relates to skeletal muscle IGF-I and mitochondrial function and gene expression in obese men with reduced growth hormone

2016 ◽  
Vol 26 ◽  
pp. 36-41 ◽  
Author(s):  
Suman Srinivasa ◽  
Caroline Suresh ◽  
Jay Mottla ◽  
Sulaiman R. Hamarneh ◽  
Javier E. Irazoqui ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Hormone ◽  
Mitochondrial Function ◽  
Igf I

Growth hormone and testosterone interact positively to enhance protein and energy metabolism in hypopituitary men

2005 ◽  
Vol 289 (2) ◽  
pp. E266-E271 ◽  
Author(s):  
James Gibney ◽  
Troels Wolthers ◽  
Gudmundur Johannsson ◽  
A. Margot Umpleby ◽  
Ken K. Y. Ho
Keyword(s):  
Growth Hormone ◽  
Protein Metabolism ◽  
Resting Energy Expenditure ◽  
Whole Body ◽  
Combined Treatments ◽  
Gh Treatment ◽  
Additional Increase ◽  
Body Protein ◽  
Igf I ◽  
The Impact

We investigated the impact of growth hormone (GH) alone, testosterone (T) alone, and combined GH and T on whole body protein metabolism. Twelve hypopituitary men participated in two studies. Study 1 compared the effects of GH alone with GH plus T, and study 2 compared the effects of T alone with GH plus T. IGF-I, resting energy expenditure (REE), and fat oxidation (Fox) and rates of whole body leucine appearance (Ra), oxidation (Lox), and nonoxidative leucine disposal (NOLD) were measured. In study 1, GH treatment increased mean plasma IGF-I ( P < 0.001). GH did not change leucine Ra but reduced Lox ( P < 0.02) and increased NOLD ( P < 0.02). Addition of T resulted in an additional increase in IGF-I ( P < 0.05), reduction in Lox ( P < 0.002), and increase in NOLD ( P < 0.002). In study 2, T alone did not alter IGF-I levels. T alone did not change leucine Ra but reduced Lox ( P < 0.01) and increased NOLD ( P < 0.01). Addition of GH further reduced Lox ( P < 0.05) and increased NOLD ( P < 0.05). In both studies, combined treatments on REE and Fox were greater than either alone. In summary, GH-induced increase of circulating IGF-I is augmented by T, which does not increase IGF-I in the absence of GH. T and GH exerted independent and additive effects on protein metabolism, Fox and REE. The anabolic effects of T are independent of circulating IGF-I.

Oral estrogen antagonizes the metabolic actions of growth hormone in growth hormone-deficient women

2001 ◽  
Vol 281 (6) ◽  
pp. E1191-E1196 ◽  
Author(s):  
Troels Wolthers ◽  
David M. Hoffman ◽  
Ailish G. Nugent ◽  
Mark W Duncan ◽  
Margot Umpleby ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Lipid Oxidation ◽  
Biological Effects ◽  
Treatment Phase ◽  
Estrogen Treatment ◽  
Whole Body ◽  
Beneficial Effects ◽  
Oral Estrogen ◽  
Igf I ◽  
Transdermal Estrogen

We have determined whether oral estrogen reduces the biological effects of growth hormone (GH) in GH-deficient (GHD) women compared with transdermal estrogen treatment. In two separate studies, eight GHD women randomly received either oral or transdermal estrogen for 8 wk before crossing over to the alternate route of administration. The first study assessed the effects of incremental doses of GH (0.5, 1.0, 2.0 IU/day for 1 wk each) on insulin-like growth factor I (IGF-I) levels during each estrogen treatment phase. The second study assessed the effects of GH (2 IU/day) on lipid oxidation and on protein metabolism using the whole body leucine turnover technique. Mean IGF-I level was significantly lower during oral estrogen treatment ( P < 0.05) and rose dose dependently during GH administration by a lesser magnitude ( P < 0.05) compared with transdermal treatment. Postprandial lipid oxidation was significantly lower with oral estrogen treatment, both before ( P < 0.05) and during ( P < 0.05) GH administration, compared with transdermal treatment. Protein synthesis was lower during oral estrogen both before and during GH administration ( P < 0.05). Oral estrogen antagonizes several of the metabolic actions of GH. It may aggravate body composition abnormalities already present in GHD women and attenuate the beneficial effects of GH therapy. Estrogen replacement in GHD women should be administered by a nonoral route.

Whole-body leucine turnover in adults on conventional treatment for hypopituitarism

1993 ◽  
Vol 129 (2) ◽  
pp. 158-164 ◽  
Author(s):  
Salem A Beshyah ◽  
Patrick S Sharp ◽  
Susan V Gelding ◽  
David Halliday ◽  
Desmond G Johnston
Keyword(s):  
Growth Hormone ◽  
Serum Insulin ◽  
Hormone Replacement ◽  
Whole Body ◽  
Leucine Incorporation ◽  
Gh Treatment ◽  
Mean Values ◽  
Growth Hormone Replacement Therapy ◽  
Igf I ◽  
Normal Controls

This study has investigated protein metabolism in adults with hypopituitarism before and after growth hormone (GH) replacement and in matched controls. Whole-body leucine turnover was measured in 16 GH-deficient adult hypopituitary patients (nine females and seven males) on standard thyroid, adrenal and sex hormone replacement and in 20 normal controls using primed continuous infusion of l-[1 – 13C]leucine. In seven of the patients, leucine turnover was restudied following 6 months' treatment with biosynthetic human GH (0.025–0.05 IU/kg body wt daily, with the final dose determined by patient tolerance). Compared with normal controls, hypopituitary patients had significantly reduced leucine flux (mean±sd: 97.8±24.9 vs 131.0±23.0 μmol·h−1·kg−1; p<0.001), reduced leucine incorporation into protein (80.4±20.9 vs 108.8±19.6 μmol·h−1·kg−1; p<0.001) and reduced leucine oxidation (17.4±4.8 vs 22.2±8.1 μmol·h−1·kg−1; p<0.05). Leucine turnover was similar in male and female patients. In the patients, leucine flux correlated positively with body weight (p = 0.51, p<0.05) and leucine incorporation in protein correlated positively with lean body mass (p = 0.55, p <0.05) and in male patients leucine flux correlated positively with serum insulin-like growth factor I (IGF-I) levels (ρ=0.71, p<0.05). No significant relationship was observed with age or duration of hypopituitarism. Growth hormone replacement therapy did not produce a uniform effect on leucine metabolism. Mean values of leucine flux, oxidation and incorporation into protein increased, although the differences were not statistically significant. The patients on higher GH doses and with a higher serum IGF-I response were those who demonstrated an increase in leucine turnover. We conclude that leucine turnover in hypopituitary adults is reduced compared with normal controls. The effect of GH treatment for 6 months at conventional doses in hypopituitary adults is not uniform and may be dose-dependent.

scholarly journals Growth Hormone Treatment Prevents the Decrease in Insulin-Like Growth Factor I Gene Expression in Patients Undergoing Abdominal Surgery1

1998 ◽  
Vol 83 (5) ◽  
pp. 1566-1572
Author(s):  
Ragnar Bjarnason ◽  
Ruth Wickelgren ◽  
Majlis Hermansson ◽  
Folke Hammarqvist ◽  
Björn Carlsson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Parenteral Nutrition ◽  
Major Surgery ◽  
Control Group ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Gh Treatment ◽  
Igf I ◽  
I Gene

Acquired GH resistance together with reduced skeletal muscle mass are found in patients with increased protein catabolism due, for example, to sepsis, trauma, or major surgery. Both administration of glutamine-containing parenteral nutrition and GH treatment have been found to diminish this catabolism. The effects of GH are mediated in part by insulin-like growth factor I (IGF-I) that is produced in the liver and locally in GH target tissues. The aim of this study was to investigate the effect of GH treatment on expression of the IGF-I gene and GH receptor (GHR) gene in skeletal muscle after major surgery. A new quantitative RT-PCR-based assay was established to measure IGF-I gene expression. Metabolically healthy patients, without significant preoperative weight loss, who were undergoing elective abdominal surgery were included in the study. Five patients (one woman and four men) were treated with daily injections of GH (0.3 IU/kg·day) in addition to being given total parenteral nutrition including glutamine (0.28 g/kg·day). The control group consisted of eight patients (three women and five men), who were given glutamine-enriched total parenteral nutrition but no GH. A muscle biopsy was taken from the lateral portion of the quadriceps femoris muscle preoperatively (day 0) after induction of anesthesia. A second biopsy was taken under local anesthesia on postoperative day 3. Total ribonucleic acid (RNA) was extracted from the muscle biopsies, and IGF-I messenger RNA (mRNA) and GHR mRNA were measured by competitive quantitative RT-PCR assays. IGF-I mRNA and GHR mRNA levels were related to the expression of a housekeeping gene (cyclophilin). In the control group, IGF-I mRNA levels decreased from 1505 ± 265 (mean ± sem) transcripts/cpm cyclophilin on day 0 to 828 ± 172 on day 3 (P &lt; 0.05). In contrast, IGF-I mRNA levels did not change in the GH-treated group (1188 ± 400 transcripts/cpm cyclophilin on day 0 vs. 1089± 342 transcripts/cpm cyclophilin on day 3). No statistically significant changes were seen in GHR expression. We conclude that administration of GH prevents the reduction in IGF-I gene expression in skeletal muscle after abdominal surgery.

Growth hormone increases IGF-I, collagen I and collagen III gene expression in dwarf rat skeletal muscle

1995 ◽  
Vol 115 (2) ◽  
pp. 187-197 ◽  
Author(s):  
Victoria J. Wilson ◽  
Marcus Rattray ◽  
Chris R. Thomas ◽  
Barbara H. Moreland ◽  
Dennis Schulster
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Hormone ◽  
Collagen I ◽  
Rat Skeletal Muscle ◽  
Collagen Iii ◽  
Igf I

Efficacy of long-term growth hormone therapy in short non-growth hormone-deficient children

2017 ◽  
Vol 30 (2) ◽  
Author(s):  
Lucia Schena ◽  
Cristina Meazza ◽  
Sara Pagani ◽  
Valeria Paganelli ◽  
Elena Bozzola ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Final Height ◽  
Standard Deviation Score ◽  
Bone Age ◽  
Gh Treatment ◽  
Short Children ◽  
Igf I ◽  
Height Gain ◽  
The Cost

AbstractBackground:In recent years, several studies have been published showing different responses to growth hormone (GH) treatment in idiopathic short stature children. The aim of the present study was to investigate whether non-growth-hormone-deficient (non-GHD) short children could benefit from long-term GH treatment as GHD patients.Methods:We enrolled 22 prepubertal children and 22 age- and sex-matched GHD patients, with comparable height, body mass index (BMI), bone age, and insulin-like growth factor 1 (IGF-I) circulating levels. The patients were treated with recombinant human GH (rhGH) and followed until they reach adult height.Results:During GH treatment, the two groups grew in parallel, reaching the same final height-standard deviation score (SDS) and the same height gain. On the contrary, we found significantly lower IGF-I serum concentrations in non-GHD patients than in GHD ones, at the end of therapy (p=0.0055).Conclusions:In our study, the response to GH treatment in short non-GHD patients proved to be similar to that in GHD ones. However, a careful selection of short non-GHD children to be treated with GH would better justify the cost of long-term GH therapy.

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