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GH administration patterns differently regulate epidermal growth factor signaling.

María E Díaz1, Johanna G Miquet, Soledad P Rossi

  • 1Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Universidad de Buenos Aires, Junín 956, 1113 Ciudad de Buenos Aires, Argentina Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490, 1428 Ciudad de Buenos Aires, Argentina.

The Journal of Endocrinology
|March 14, 2014
PubMed
Summary

Sustained growth hormone (GH) delivery may improve treatment safety. Continuous GH plasma patterns in males reduced liver epidermal growth factor receptor (EGFR) signaling, unlike intermittent injections in females.

Keywords:
epidermal growth factorgrowth hormoneintracellular signalingliver

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Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Current growth hormone (GH) administration requires frequent injections, impacting patient compliance.
  • GH's diverse effects depend on plasma concentration patterns (pulsatile vs. continuous).
  • Epidermal growth factor receptor (EGFR) dysregulation is linked to various cancers, and GH may influence its expression.

Purpose of the Study:

  • To investigate the impact of different growth hormone (GH) plasma concentration patterns on liver epidermal growth factor receptor (EGFR) expression and signaling.
  • To assess the potential link between GH administration methods and cancer-related signaling pathways.

Main Methods:

  • Administered GH via daily subcutaneous injections to simulate intermittent plasma levels.
  • Utilized osmotic pumps for continuous GH delivery, creating sustained elevated plasma concentrations.
  • Analyzed EGFR expression, EGF-induced signaling, and related gene expression in mouse liver tissues.

Main Results:

  • Intermittent GH injections upregulated liver EGFR and enhanced EGF response in female mice, promoting cell proliferation markers.
  • Continuous GH delivery in male mice downregulated liver EGFR and diminished EGF-induced signaling.
  • Sex-specific differences in GH's effect on EGFR signaling were observed.

Conclusions:

  • Sustained-release GH delivery systems creating continuous plasma patterns may offer improved safety by modulating EGFR signaling.
  • Continuous GH administration could mitigate the pro-proliferative effects of GH on liver EGFR, potentially reducing cancer risk.