GH directly stimulates UCP3 expression

Growth Horm IGF Res. 2018 Jun:40:44-54. doi: 10.1016/j.ghir.2018.01.002. Epub 2018 Jan 31.

Abstract

Objective: We evaluated the direct action of GH signaling in energy homeostasis in myocytes.

Design: We investigated the GH-induced expression of UCP3 in human embryonic kidney 293 cells, human H-EMC-SS chondrosarcoma cells, murine C2C12 skeletal muscle myoblasts, and rat L6 skeletal muscle cells, as well as its direct effect on the GHR/JAK/STAT5 pathway using a combination of a reporter assay, real-time quantitative polymerase chain reaction, and western blotting.

Results: We demonstrated that the regulation of energy metabolism by GH involves UCP3 via activated STAT5, a signal transducer downstream of GH. UCP3 expression increased with STAT5 in a dose-dependent manner and was higher than that of UCP2. We confirmed the functional STAT5 binding site consensus sequences at -861 and -507 bp in the UCP3 promoter region.

Conclusion: The results suggest that GH stimulates UCP3 directly and that UCP2 and that UCP3 participate in the signal transduction pathway that functions downstream of the GHR/JAK/STAT.

Keywords: Energy metabolism; Muscle specific gene; Signal transduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Chondrosarcoma / genetics
  • Chondrosarcoma / metabolism*
  • Chondrosarcoma / pathology
  • Gene Expression Regulation / drug effects*
  • Growth Hormone / pharmacology*
  • Humans
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / metabolism
  • Mice
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism*
  • Myoblasts, Skeletal / cytology
  • Myoblasts, Skeletal / metabolism*
  • Rats
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / metabolism
  • Signal Transduction
  • Uncoupling Protein 3 / genetics
  • Uncoupling Protein 3 / metabolism*

Substances

  • STAT5 Transcription Factor
  • Uncoupling Protein 3
  • Growth Hormone
  • Janus Kinase 2