Protein turnover in rat skeletal muscle: effects of hypophysectomy and growth hormone.

The role of growth hormone in regulating protein turnover was examined in a perfused preparation of rat skeletal muscle. The perfused muscle maintained in vivo levels of ATP and creatine phosphate and exhibited constant rates of oxygen consumption and protein synthesis. Hypophysectomy reduced the rate of protein synthesis, the concentration of RNA, and the efficiency of protein synthesis in gastrocnemius muscle to 30, 46, and 66 percent of normal, respectively. In vivo treatment of hypophysectomized (hypox) rats with bovine growth hormone (250 microgram/day for 5 days) resulted in small increases in protein synthesis and RNA, whereas synthesis/RNA was returned to near normal. Elevation of ribosomal subunits in psoas muscle indicated an inhibition of peptide-chain initiation in hypox rats that was reversed by in vivo growth hormone treatment. Thus, hypox rats exhibited both a decreased capacity and a decreased efficiency of protein synthesis. Growth hormone replacement primarily increased efficiency of protein synthesis. The rate of protein degradation and the activity of cathepsin D in gastrocnemius muscle were decreased by hypophysectomy. Growth hormone treatment had no significant effect on degradation.

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In vivo growth hormone treatment rapidly stimulates the tyrosine phosphorylation and activation of Stat3.

Molecular Endocrinology ◽

10.1210/mend.9.2.7776967 ◽

1995 ◽

Vol 9 (2) ◽

pp. 171-177 ◽

Cited By ~ 3

Author(s):

A M Gronowski ◽

Z Zhong ◽

Z Wen ◽

M J Thomas ◽

J E Darnell ◽

...

Keyword(s):

Growth Hormone ◽

Tyrosine Phosphorylation ◽

Growth Hormone Treatment ◽

Hormone Treatment ◽

In Vivo Growth

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Protein synthesis in skeletal muscle of the perfused rat hemicorpus compared with rates in the intact animal

Biochemical Journal ◽

10.1042/bj2140433 ◽

1983 ◽

Vol 214 (2) ◽

pp. 433-442 ◽

Cited By ~ 25

Author(s):

V R Preedy ◽

P J Garlick

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Gastrocnemius Muscle ◽

Intact Animal ◽

Rna Content ◽

Isolated Rat

The rate of protein synthesis was measured in muscles of the perfused rat hemicorpus, and values were compared with rates obtained in whole animals. In gastrocnemius muscle of fed rats the rate of synthesis measured in the hemicorpus was the same as that in the whole animal. However, in plantaris, quadriceps and soleus muscles rates were higher in the hemicorpus than those in vivo. In the hemicorpus, starvation for 1 day decreased the rate of protein synthesis in gastrocnemius and plantaris muscles, in parallel with decreases in the RNA content, but the soleus remained unaffected. Similar effects of starvation were observed in vivo, so that the relationships between rates in vivo and in the hemicorpus were the same as those in fed rats. Proteins of quadriceps and plantaris muscles were separated into sarcoplasmic and myofibrillar fractions. The rate of synthesis in the sarcoplasmic fraction of the hemicorpus from fed rats was similar to that in vivo, but synthesis in the myofibrillar fraction was greater. In the plantaris of starved rats the rates of synthesis in both fractions were lower, but the relationships between rates measured in vivo and in the perfused hemicorpus were similar to those seen in fed rats. The addition of insulin to the perfusate of the hemicorpus prepared from 1-day-starved animals increased the rates of protein synthesis per unit of RNA in gastrocnemius and plantaris muscles to values above those seen in fed animals when measured in vivo or in the hemicorpus. Insulin had no effect on the soleus. Overall, the rates of protein synthesis in the hemicorpus differed from those in vivo. However, the effect of starvation when measured in the whole animal was very similar to that measured in the isolated rat hemicorpus when insulin was omitted from the perfusate.

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Effects of Caloric Restriction and Growth Hormone Treatment on Insulin‐Related Intermediates in The Skeletal Muscle

The FASEB Journal ◽

10.1096/fasebj.22.2_supplement.116 ◽

2008 ◽

Vol 22 (S2) ◽

pp. 116-116

Author(s):

Khalid A Al‐Regaiey ◽

Michal M Masternak ◽

Zhihui Wang ◽

Jacob Panici ◽

Andrzej Bartke

Keyword(s):

Skeletal Muscle ◽

Growth Hormone ◽

Caloric Restriction ◽

Growth Hormone Treatment ◽

Hormone Treatment

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Rapid changes in nuclear protein tyrosine phosphorylation after growth hormone treatment in vivo. Identification of phosphorylated mitogen-activated protein kinase and STAT91.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)37132-6 ◽

1994 ◽

Vol 269 (11) ◽

pp. 7874-7878 ◽

Cited By ~ 3

Author(s):

A.M. Gronowski ◽

P. Rotwein

Keyword(s):

Growth Hormone ◽

Protein Kinase ◽

Growth Hormone Treatment ◽

Nuclear Protein ◽

Hormone Treatment ◽

Mitogen Activated Protein Kinase ◽

Protein Tyrosine Phosphorylation ◽

Rapid Changes ◽

Mitogen Activated Protein

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3-27-05 Growth hormone treatment in GH deficient adults: Effects on skeletal muscle and exercise

Journal of the Neurological Sciences ◽

10.1016/s0022-510x(97)85731-0 ◽

1997 ◽

Vol 150 ◽

pp. S178

Author(s):

A. Leal-Cerro ◽

J. Guerra ◽

D. Segura ◽

I. Chinchón ◽

E. Rafel ◽

...

Keyword(s):

Skeletal Muscle ◽

Growth Hormone ◽

Growth Hormone Treatment ◽

Hormone Treatment

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REDD1 deletion prevents dexamethasone-induced skeletal muscle atrophy

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00234.2014 ◽

2014 ◽

Vol 307 (11) ◽

pp. E983-E993 ◽

Cited By ~ 49

Author(s):

Florian A. Britto ◽

Gwenaelle Begue ◽

Bernadette Rossano ◽

Aurélie Docquier ◽

Barbara Vernus ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Muscle Mass ◽

Tibialis Anterior ◽

Skeletal Muscle Mass ◽

Gastrocnemius Muscle ◽

Mtorc1 Signaling ◽

Inhibition Of Protein Synthesis ◽

Stress Dependent

REDD1 (regulated in development and DNA damage response 1) has been proposed to inhibit the mechanistic target of rapamycin complex 1 (mTORC1) during in vitro hypoxia. REDD1 expression is low under basal conditions but is highly increased in response to several catabolic stresses, like hypoxia and glucocorticoids. However, REDD1 function seems to be tissue and stress dependent, and its role in skeletal muscle in vivo has been poorly characterized. Here, we investigated the effect of REDD1 deletion on skeletal muscle mass, protein synthesis, proteolysis, and mTORC1 signaling pathway under basal conditions and after glucocorticoid administration. Whereas skeletal muscle mass and typology were unchanged between wild-type (WT) and REDD1-null mice, oral gavage with dexamethasone (DEX) for 7 days reduced tibialis anterior and gastrocnemius muscle weights as well as tibialis anterior fiber size only in WT. Similarly, REDD1 deletion prevented the inhibition of protein synthesis and mTORC1 activity (assessed by S6, 4E-BP1, and ULK1 phosphorylation) observed in gastrocnemius muscle of WT mice following single DEX administration for 5 h. However, our results suggest that REDD1-mediated inhibition of mTORC1 in skeletal muscle is not related to the modulation of the binding between TSC2 and 14-3-3. In contrast, our data highlight a new mechanism involved in mTORC1 inhibition linking REDD1, Akt, and PRAS40. Altogether, these results demonstrated in vivo that REDD1 is required for glucocorticoid-induced inhibition of protein synthesis via mTORC1 downregulation. Inhibition of REDD1 may thus be a strategy to limit muscle loss in glucocorticoid-mediated atrophy.

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