TY - JOUR

T1 - GH signaling in skeletal muscle and adipose tissue in healthy human subjects

T2 - impact of gender and age

AU - Vestergaard, Poul F

AU - Vendelbo, Mikkel H

AU - Pedersen, Steen B

AU - Juul, Anders

AU - Ringgard, Steffen

AU - Møller, Niels

AU - Jessen, Niels

AU - Jørgensen, Jens O L

N1 - © 2014 European Society of Endocrinology.

PY - 2014/11

Y1 - 2014/11

N2 - OBJECTIVE: The mechanisms underlying the impact of age and gender on the GH-IGF1 axis remain unclear. We tested the hypothesis that age and gender have impacts on GH signaling in human subjects in vivo.DESIGN: A total of 20 healthy non-obese adults ('young group'<30 years (5F/5M) and 'old group'>60 years (5F/5M)) were studied after: i) an i.v. GH bolus (0.5 mg) and ii) saline.METHODS: Muscle and fat biopsies were obtained after 30 and 120 min. Total and phosphorylated STAT5B proteins, gene expression of IGF1, SOCS1, SOCS2, SOCS3 and CISH, body composition, VO2max, and muscle strength were measured.RESULTS: In the GH-unstimulated state, women displayed significantly elevated levels of CISH mRNA in muscle (P=0.002) and fat (P=0.05) and reduced levels of IGF1 mRNA in fat. Phosphorylated STAT5B (pSTAT5b) was maximally increased in all subjects 30 min after GH exposure and more pronounced in women when compared with men (P=0.01). IGF1, SOCS1, SOCS2, SOCS3, and CISH mRNA expression increased significantly in muscle after 120 min in all subjects with no impact of age and gender. GH-induced pSTAT5b correlated inversely with lean body mass (LBM; r=-0.56, P=0.01) and positively with the CISH mRNA response (r=0.533, P=0.05).CONCLUSION: i) GH signaling in muscle and fat after a single GH bolus in healthy human subjects is age independent, ii) we hypothesize that constitutive overexpression of CISH may contribute to the relative GH resistance in women, and iii) experimental studies on the impact of sex steroid administration and physical training on GH signaling in human subjects in vivo are required.

AB - OBJECTIVE: The mechanisms underlying the impact of age and gender on the GH-IGF1 axis remain unclear. We tested the hypothesis that age and gender have impacts on GH signaling in human subjects in vivo.DESIGN: A total of 20 healthy non-obese adults ('young group'<30 years (5F/5M) and 'old group'>60 years (5F/5M)) were studied after: i) an i.v. GH bolus (0.5 mg) and ii) saline.METHODS: Muscle and fat biopsies were obtained after 30 and 120 min. Total and phosphorylated STAT5B proteins, gene expression of IGF1, SOCS1, SOCS2, SOCS3 and CISH, body composition, VO2max, and muscle strength were measured.RESULTS: In the GH-unstimulated state, women displayed significantly elevated levels of CISH mRNA in muscle (P=0.002) and fat (P=0.05) and reduced levels of IGF1 mRNA in fat. Phosphorylated STAT5B (pSTAT5b) was maximally increased in all subjects 30 min after GH exposure and more pronounced in women when compared with men (P=0.01). IGF1, SOCS1, SOCS2, SOCS3, and CISH mRNA expression increased significantly in muscle after 120 min in all subjects with no impact of age and gender. GH-induced pSTAT5b correlated inversely with lean body mass (LBM; r=-0.56, P=0.01) and positively with the CISH mRNA response (r=0.533, P=0.05).CONCLUSION: i) GH signaling in muscle and fat after a single GH bolus in healthy human subjects is age independent, ii) we hypothesize that constitutive overexpression of CISH may contribute to the relative GH resistance in women, and iii) experimental studies on the impact of sex steroid administration and physical training on GH signaling in human subjects in vivo are required.

KW - Adipose Tissue

KW - Adult

KW - Age Factors

KW - Aged

KW - Aged, 80 and over

KW - Female

KW - Human Growth Hormone

KW - Humans

KW - Male

KW - Middle Aged

KW - Muscle, Skeletal

KW - Sex Factors

KW - Signal Transduction

KW - Young Adult

U2 - 10.1530/EJE-14-0538

DO - 10.1530/EJE-14-0538

M3 - Journal article

C2 - 25163724

VL - 171

SP - 623

EP - 631

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

SN - 0804-4643

IS - 5

ER -