GH receptor signaling in skeletal muscle and adipose tissue in human subjects following exposure to an intravenous GH bolus

• Published in: American journal of physiology: endocrinology and metabolism Vol. 291; no. 5; pp. E899 - E905
• Main Authors: Jorgensen, Jens O. L, Jessen, Niels, Pedersen, Steen B, Vestergaard, Esben, Gormsen, Lars, Lund, Sten A, Billestrup, Nils
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.11.2006
• Subjects: Adipose tissue; Adult; Biopsy; Deoxyribonucleic acid; DNA; Gene expression; Growth hormones; Human Growth Hormone - administration & dosage; Humans; Injections, Intravenous; Insulin; Male; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Membrane Proteins - metabolism; Muscle, Skeletal - cytology; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscular system; Oils & fats; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation - drug effects; Proteins; Proto-Oncogene Proteins c-akt - metabolism; RNA, Messenger - metabolism; Signal transduction; Signal Transduction - drug effects; Signal Transduction - physiology; STAT5 Transcription Factor - metabolism; Stomach; Subcutaneous Fat - cytology; Subcutaneous Fat - drug effects; Subcutaneous Fat - metabolism; Suppressor of Cytokine Signaling 1 Protein; Suppressor of Cytokine Signaling Proteins - genetics; Tyrosine - metabolism
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00024.2006

Aarhus University Hospital and Institute of Clinical Research, Aarhus University, Aarhus, and Steno Diabetes Center, Copenhagen, Denmark Submitted 18 January 2006 ; accepted in final form 30 May 2006 Growth hormone (GH) regulates muscle and fat metabolism, which impacts on body composition and insulin sensitivty, but the underlying GH signaling pathways have not been studied in vivo in humans. We investigated GH signaling in biopsies from muscle and abdominal fat obtained 30 ( n = 3) or 60 ( n = 3) min after an intravenous bolus of GH (0.5 mg) vs. saline in conjunction with serum sampling in six healthy males after an overnight fast. Expression of the following signal proteins were assayed by Western blotting: STAT5/p-STAT5, MAPK, and Akt/PKB. IRS-1-associated PI 3-kinase activity was measured by in vitro phosphorylation of PI. STAT5 DNA binding activity was assessed with EMSA, and the expression of IGF-I and SOCS mRNA was measured by real-time RT-PCR. GH induced a 52% increase in circulating FFA levels with peak values after 155 min ( P = 0.03). Tyrosine-phosphorylated STAT5 was detected in muscle and fat of all subjects after GH. Activation of MAPK was observed in several lysates but without GH dependency. Neither PKB/Akt nor PI 3-kinase activity was affected by GH. GH-induced STAT5 DNA binding and expression of IGF-I mRNA were detected in fat, whereas expression of SOCS-1 and -3 tended to increase after GH in muscle and fat, respectively. We conclude that 1 ) STAT5 is acutely activated in human muscle and fat after a GH bolus, but additional downstream GH signaling was significant only in fat; 2 ) the direct GH effects in muscle need further characterization; and 3 ) this human in vivo model may be used to study the mechanisms subserving the actions of GH on substrate metabolism and insulin sensitivity in muscle and fat. growth hormone; signal transducer and activator of transcription 5; suppressor of cytokine signaling; insulin-like growth factor I; signaling Address for reprint requests and other correspondence: J. O. L. Jørgensen, Medical Dept. M, Aarhus University Hospital, Norrebrogade 44, DK-8000 C, Aarhus, Denmark (e-mail: joj{at}afdm.au.dk )