Testosterone deficiency in young men: Marked alterations in whole body protein kinetics, strength, and adiposity

Nelly Mauras, Valerie Hayes, Susan Welch, Annie Rini, Kevin Helgeson, Maryanne Dokler, Johannes D. Veldhuis, Randall Urban

Research output: Contribution to journalArticle

317 Citations (Scopus)

Abstract

To investigate specific effects of androgens on whole body metabolism, we studied six healthy lean men (mean ± SEM age, 23.2 ± 0.5 yr) before and after gonadal steroid suppression with a GnRH analog (Lupron), given twice, 3 weeks apart. Primed infusions of [13C]leucine, indirect calorimetry, isokinetic dynamometry, growth factor measurements, and percutaneous muscle biopsies were performed at baseline (D1) and after 10 weeks of treatment (D2); each subject served as his own control. Testosterone concentrations were markedly suppressed after 10 weeks of treatment (D1, 535 ± 141 ng/dL; D2, 31 ± 9). Leucine's rate of appearance (index of proteolysis) was markedly suppressed after 10 weeks of hypogonadism (-13%; P = 0.01) as well as the nonoxidative leucine disposal, an index of whole body protein synthesis (-13%; P = 0.01) without any changes in plasma amino acid concentrations. All subjects studied after 10 weeks showed a decrease in fat- free mass, as measured by skinfold calipers and dual emission x-ray absortiometry scans (D1, 56.5 ± 2.9 kg; D2, 54.4 ± 2.5; P = 0.005), and an increase in percent fat mass (D1, 19.2 ± 2.5%; D2, 22.2 ± 2.5; P = 0.001). Rates of lipid oxidation decreased (-31%; P = 0.05) after treatment, with parallel changes in resting energy expenditure (-9%; P = 0.05). Mean and peak GH concentrations (measured every 10 min for 6 h) and GH production rates did not decrease after testosterone deficiency, with an actual increase in basal secretion (P < 0.02). Plasma insulin-like growth factor I (IGF-I) concentrations did not change significantly after 10 weeks of treatment (D1, 227 ± 44 μg/L; D2, 291 ± 60; P = 0.08). Isokinetic dynamometry of leg extensors at 60°and 180°/s was also decreased after 10 weeks of hypogonadism. Total ribonucleic acid (RNA) was isolated from muscle biopsy samples, and ribonuclease protection assays were performed using human complementary DNA clones for IGF-I, IGF-binding protein-4, myosin, and actin. Ten weeks after Lupron treatment, messenger RNA (mRNA) concentrations of IGF- I decreased significantly, whereas there was a trend toward higher IGF- binding protein-4 concentrations, with no change in myosin or actin mRNA concentrations. In conclusion, testosterone deficiency in young men is associated with a marked decrease in measures of whole body protein anabotism, decreased strength, decreased fat oxidation, and increased adiposity. These effects of testosterone deficiency are independent of changes in peripheral GH production and IGF-I concentrations, even though im IGF-I mRNA concentrations decrease. These data suggest a direct effect of androgens on whole body lipid and protein metabolism.

Original languageEnglish (US)
Pages (from-to)1886-1892
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume83
Issue number6
DOIs
StatePublished - 1998

Fingerprint

Adiposity
Insulin-Like Growth Factor I
Testosterone
Kinetics
Insulin-Like Growth Factor Binding Protein 4
Leucine
Leuprolide
Hypogonadism
Biopsy
Fats
Myosins
Proteins
Metabolism
Androgens
Muscle
Actins
RNA
Proteolysis
Body Weights and Measures
Lipids

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Testosterone deficiency in young men : Marked alterations in whole body protein kinetics, strength, and adiposity. / Mauras, Nelly; Hayes, Valerie; Welch, Susan; Rini, Annie; Helgeson, Kevin; Dokler, Maryanne; Veldhuis, Johannes D.; Urban, Randall.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 83, No. 6, 1998, p. 1886-1892.

Research output: Contribution to journalArticle

Mauras, Nelly ; Hayes, Valerie ; Welch, Susan ; Rini, Annie ; Helgeson, Kevin ; Dokler, Maryanne ; Veldhuis, Johannes D. ; Urban, Randall. / Testosterone deficiency in young men : Marked alterations in whole body protein kinetics, strength, and adiposity. In: Journal of Clinical Endocrinology and Metabolism. 1998 ; Vol. 83, No. 6. pp. 1886-1892.
@article{b21d51c215d9433e8496a8c813ac5ff4,
title = "Testosterone deficiency in young men: Marked alterations in whole body protein kinetics, strength, and adiposity",
abstract = "To investigate specific effects of androgens on whole body metabolism, we studied six healthy lean men (mean ± SEM age, 23.2 ± 0.5 yr) before and after gonadal steroid suppression with a GnRH analog (Lupron), given twice, 3 weeks apart. Primed infusions of [13C]leucine, indirect calorimetry, isokinetic dynamometry, growth factor measurements, and percutaneous muscle biopsies were performed at baseline (D1) and after 10 weeks of treatment (D2); each subject served as his own control. Testosterone concentrations were markedly suppressed after 10 weeks of treatment (D1, 535 ± 141 ng/dL; D2, 31 ± 9). Leucine's rate of appearance (index of proteolysis) was markedly suppressed after 10 weeks of hypogonadism (-13{\%}; P = 0.01) as well as the nonoxidative leucine disposal, an index of whole body protein synthesis (-13{\%}; P = 0.01) without any changes in plasma amino acid concentrations. All subjects studied after 10 weeks showed a decrease in fat- free mass, as measured by skinfold calipers and dual emission x-ray absortiometry scans (D1, 56.5 ± 2.9 kg; D2, 54.4 ± 2.5; P = 0.005), and an increase in percent fat mass (D1, 19.2 ± 2.5{\%}; D2, 22.2 ± 2.5; P = 0.001). Rates of lipid oxidation decreased (-31{\%}; P = 0.05) after treatment, with parallel changes in resting energy expenditure (-9{\%}; P = 0.05). Mean and peak GH concentrations (measured every 10 min for 6 h) and GH production rates did not decrease after testosterone deficiency, with an actual increase in basal secretion (P < 0.02). Plasma insulin-like growth factor I (IGF-I) concentrations did not change significantly after 10 weeks of treatment (D1, 227 ± 44 μg/L; D2, 291 ± 60; P = 0.08). Isokinetic dynamometry of leg extensors at 60°and 180°/s was also decreased after 10 weeks of hypogonadism. Total ribonucleic acid (RNA) was isolated from muscle biopsy samples, and ribonuclease protection assays were performed using human complementary DNA clones for IGF-I, IGF-binding protein-4, myosin, and actin. Ten weeks after Lupron treatment, messenger RNA (mRNA) concentrations of IGF- I decreased significantly, whereas there was a trend toward higher IGF- binding protein-4 concentrations, with no change in myosin or actin mRNA concentrations. In conclusion, testosterone deficiency in young men is associated with a marked decrease in measures of whole body protein anabotism, decreased strength, decreased fat oxidation, and increased adiposity. These effects of testosterone deficiency are independent of changes in peripheral GH production and IGF-I concentrations, even though im IGF-I mRNA concentrations decrease. These data suggest a direct effect of androgens on whole body lipid and protein metabolism.",
author = "Nelly Mauras and Valerie Hayes and Susan Welch and Annie Rini and Kevin Helgeson and Maryanne Dokler and Veldhuis, {Johannes D.} and Randall Urban",
year = "1998",
doi = "10.1210/jc.83.6.1886",
language = "English (US)",
volume = "83",
pages = "1886--1892",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "6",

}

TY - JOUR

T1 - Testosterone deficiency in young men

T2 - Marked alterations in whole body protein kinetics, strength, and adiposity

AU - Mauras, Nelly

AU - Hayes, Valerie

AU - Welch, Susan

AU - Rini, Annie

AU - Helgeson, Kevin

AU - Dokler, Maryanne

AU - Veldhuis, Johannes D.

AU - Urban, Randall

PY - 1998

Y1 - 1998

N2 - To investigate specific effects of androgens on whole body metabolism, we studied six healthy lean men (mean ± SEM age, 23.2 ± 0.5 yr) before and after gonadal steroid suppression with a GnRH analog (Lupron), given twice, 3 weeks apart. Primed infusions of [13C]leucine, indirect calorimetry, isokinetic dynamometry, growth factor measurements, and percutaneous muscle biopsies were performed at baseline (D1) and after 10 weeks of treatment (D2); each subject served as his own control. Testosterone concentrations were markedly suppressed after 10 weeks of treatment (D1, 535 ± 141 ng/dL; D2, 31 ± 9). Leucine's rate of appearance (index of proteolysis) was markedly suppressed after 10 weeks of hypogonadism (-13%; P = 0.01) as well as the nonoxidative leucine disposal, an index of whole body protein synthesis (-13%; P = 0.01) without any changes in plasma amino acid concentrations. All subjects studied after 10 weeks showed a decrease in fat- free mass, as measured by skinfold calipers and dual emission x-ray absortiometry scans (D1, 56.5 ± 2.9 kg; D2, 54.4 ± 2.5; P = 0.005), and an increase in percent fat mass (D1, 19.2 ± 2.5%; D2, 22.2 ± 2.5; P = 0.001). Rates of lipid oxidation decreased (-31%; P = 0.05) after treatment, with parallel changes in resting energy expenditure (-9%; P = 0.05). Mean and peak GH concentrations (measured every 10 min for 6 h) and GH production rates did not decrease after testosterone deficiency, with an actual increase in basal secretion (P < 0.02). Plasma insulin-like growth factor I (IGF-I) concentrations did not change significantly after 10 weeks of treatment (D1, 227 ± 44 μg/L; D2, 291 ± 60; P = 0.08). Isokinetic dynamometry of leg extensors at 60°and 180°/s was also decreased after 10 weeks of hypogonadism. Total ribonucleic acid (RNA) was isolated from muscle biopsy samples, and ribonuclease protection assays were performed using human complementary DNA clones for IGF-I, IGF-binding protein-4, myosin, and actin. Ten weeks after Lupron treatment, messenger RNA (mRNA) concentrations of IGF- I decreased significantly, whereas there was a trend toward higher IGF- binding protein-4 concentrations, with no change in myosin or actin mRNA concentrations. In conclusion, testosterone deficiency in young men is associated with a marked decrease in measures of whole body protein anabotism, decreased strength, decreased fat oxidation, and increased adiposity. These effects of testosterone deficiency are independent of changes in peripheral GH production and IGF-I concentrations, even though im IGF-I mRNA concentrations decrease. These data suggest a direct effect of androgens on whole body lipid and protein metabolism.

AB - To investigate specific effects of androgens on whole body metabolism, we studied six healthy lean men (mean ± SEM age, 23.2 ± 0.5 yr) before and after gonadal steroid suppression with a GnRH analog (Lupron), given twice, 3 weeks apart. Primed infusions of [13C]leucine, indirect calorimetry, isokinetic dynamometry, growth factor measurements, and percutaneous muscle biopsies were performed at baseline (D1) and after 10 weeks of treatment (D2); each subject served as his own control. Testosterone concentrations were markedly suppressed after 10 weeks of treatment (D1, 535 ± 141 ng/dL; D2, 31 ± 9). Leucine's rate of appearance (index of proteolysis) was markedly suppressed after 10 weeks of hypogonadism (-13%; P = 0.01) as well as the nonoxidative leucine disposal, an index of whole body protein synthesis (-13%; P = 0.01) without any changes in plasma amino acid concentrations. All subjects studied after 10 weeks showed a decrease in fat- free mass, as measured by skinfold calipers and dual emission x-ray absortiometry scans (D1, 56.5 ± 2.9 kg; D2, 54.4 ± 2.5; P = 0.005), and an increase in percent fat mass (D1, 19.2 ± 2.5%; D2, 22.2 ± 2.5; P = 0.001). Rates of lipid oxidation decreased (-31%; P = 0.05) after treatment, with parallel changes in resting energy expenditure (-9%; P = 0.05). Mean and peak GH concentrations (measured every 10 min for 6 h) and GH production rates did not decrease after testosterone deficiency, with an actual increase in basal secretion (P < 0.02). Plasma insulin-like growth factor I (IGF-I) concentrations did not change significantly after 10 weeks of treatment (D1, 227 ± 44 μg/L; D2, 291 ± 60; P = 0.08). Isokinetic dynamometry of leg extensors at 60°and 180°/s was also decreased after 10 weeks of hypogonadism. Total ribonucleic acid (RNA) was isolated from muscle biopsy samples, and ribonuclease protection assays were performed using human complementary DNA clones for IGF-I, IGF-binding protein-4, myosin, and actin. Ten weeks after Lupron treatment, messenger RNA (mRNA) concentrations of IGF- I decreased significantly, whereas there was a trend toward higher IGF- binding protein-4 concentrations, with no change in myosin or actin mRNA concentrations. In conclusion, testosterone deficiency in young men is associated with a marked decrease in measures of whole body protein anabotism, decreased strength, decreased fat oxidation, and increased adiposity. These effects of testosterone deficiency are independent of changes in peripheral GH production and IGF-I concentrations, even though im IGF-I mRNA concentrations decrease. These data suggest a direct effect of androgens on whole body lipid and protein metabolism.

UR - http://www.scopus.com/inward/record.url?scp=0031733473&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031733473&partnerID=8YFLogxK

U2 - 10.1210/jc.83.6.1886

DO - 10.1210/jc.83.6.1886

M3 - Article

C2 - 9626114

AN - SCOPUS:0031733473

VL - 83

SP - 1886

EP - 1892

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 6

ER -