GH receptor signaling in skeletal muscle and adipose tissue in human subjects following exposure to an intravenous GH bolus
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
GH receptor signaling in skeletal muscle and adipose tissue in human subjects following exposure to an intravenous GH bolus. / Jørgensen, Jens O L; Jessen, Niels; Pedersen, Steen Bønløkke; Vestergaard, Esben Thyssen; Gormsen, Lars Christian; Lund, Sten; Billestrup, Nils.
I: American Journal of Physiology: Endocrinology and Metabolism, Bind 291, Nr. 5, 01.11.2006, s. E899-905.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - GH receptor signaling in skeletal muscle and adipose tissue in human subjects following exposure to an intravenous GH bolus
AU - Jørgensen, Jens O L
AU - Jessen, Niels
AU - Pedersen, Steen Bønløkke
AU - Vestergaard, Esben Thyssen
AU - Gormsen, Lars Christian
AU - Lund, Sten
AU - Billestrup, Nils
PY - 2006/11/1
Y1 - 2006/11/1
N2 - Growth hormone (GH) regulates muscle and fat metabolism, which impacts on body composition and insulin sensitivity, 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.
AB - Growth hormone (GH) regulates muscle and fat metabolism, which impacts on body composition and insulin sensitivity, 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.
KW - Adult
KW - Biopsy
KW - Human Growth Hormone
KW - Humans
KW - Injections, Intravenous
KW - MAP Kinase Signaling System
KW - Male
KW - Membrane Proteins
KW - Muscle, Skeletal
KW - Phosphatidylinositol 3-Kinases
KW - Phosphorylation
KW - Proto-Oncogene Proteins c-akt
KW - RNA, Messenger
KW - STAT5 Transcription Factor
KW - Signal Transduction
KW - Subcutaneous Fat
KW - Suppressor of Cytokine Signaling Proteins
KW - Tyrosine
U2 - 10.1152/ajpendo.00024.2006
DO - 10.1152/ajpendo.00024.2006
M3 - Journal article
C2 - 16757551
VL - 291
SP - E899-905
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
SN - 0193-1849
IS - 5
ER -
ID: 33903289