GH signaling in skeletal muscle and adipose tissue in healthy human subjects: impact of gender and age

Abstract

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' O60 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, VO 2max , and muscle strength were measured. Results: In the GH-unstimulated state, women displayed significantly elevated levels of CISH mRNA in muscle (PZ0.002) and fat (PZ0.05) 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 (PZ0.01). 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; rZK0.56, PZ0.01) and positively with the CISH mRNA response (rZ0.533, PZ0.05). 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.

The acute effects of growth hormone in adipose tissue is associated with suppression of antilipolytic signals

“…Phosphorylation of STAT5 (pSTAT5) 30 min after GH was detected in seven of nine subjects (Figure a), but no pSTAT5 bands were detected 120 min after either GH or saline. Data on circulating GH and FFA levels from the entire study population have been reported previously (Vestergaard et al, ); in this study, we extracted data from the eight subjects, who contributed to microarray analysis. GH peaked in serum 5 min after its administration [95.1 ± 4.9 ug/l (mean ± SE)], and returned to baseline after 120 min (Figure b).…”

“…The human data derive from a clinical experiment from which data of a different nature have been published (Vestergaard et al, ). All subjects were studied in random order on two occasions after an overnight fast for 12 hr receiving an intravenous bolus of either GH (0.5 mg (Genotropin miniquick, Pfizer)) or saline.…”

Temporal patterns of lipolytic regulators in adipose tissue after acute growth hormone exposure in human subjects: A randomized controlled crossover trial

“…This temporal pattern suggests that the effect involves regulation of gene expression in AT. We have consistently demonstrated that systemic GH acutely activates the STAT5 signaling pathway, which is considered the canonical pathway whereby GH regulates transcription of target genes [5], in human AT in vivo [6], [7], [8], [9], [10], [11]. In support of this, studies in rodents indicate that STAT5 is involved in GH-induced lipolysis [12], [13], [14], [15], but there are also in vitro studies to suggest that GH stimulates lipolysis via activation of the MAPK pathway [16], [17].…”

Growth Hormone Replacement Therapy in Patients without Adult Growth Hormone Deficiency: What Answers Do We Have So Far?

“…Both spontaneous and stimulated GH secretion in middle-aged adults is determined more by abdominal fat than by aging, so weight loss would help restore impaired GH secretion in obesity [8].…”