Thyrotropin Releasing Hormone (TRH) Affects Gene Expression in Pancreatic β-Cells

Abstract

Thyrotropin-releasing hormone (TRH), originally identified as a hypothalamic hormone, is expressed in the pancreas. The peptide has been shown to control glycemia, although the role of TRH in the pancreas has not yet been clarified. In quiescent INS-1 cells (rat immortalized β-cell line), 200 nM of TRH for 24 hours significantly increased insulin levels in the culture medium and in cell extracts. In studies with gene array technology where about 60% to 75% of the 1081 genes were detected, TRH significantly stimulated multiple groups of gene expressions, including G‐protein-coupled receptor and related signaling, such as insulin secretion, endoplasmic reticulum traffic mechanisms, cell-cycle regulators, protein turnover factors, DNA recombination, and growth factors. Noticeably, TRH suppressed the genes of proapoptotic Bcl-2-associated protein X, Bcl-xL/Bcl-2-associated death promoter, and Fas. The multiple gene expressions in response to TRH in pancreatic β cells suggest that the changed microenvironment brought about by TRH may influence β-cell function.

Keywords:

• TRH
• Gene array
• Insulin
• Apoptosis
• Growth factor
• Pancreatic beta cells

ACKNOWLEDGMENTS

This work was supported in part by the Roger William Hospital Research Foundation and the National Institutes of Health COBRE program lead by Dr. Peter Quesenberry.