Effect of thyrotropin releasing hormone (TRH) on gene expressions in rat pancreas: approach by microarray hybridization.
BACKGROUND
Thyrotropin releasing hormone (TRH), originally identified as a hypothalamic hormone, expresses in the pancreas. The effects of TRH such as, inhibiting amylase secretion in rats through a direct effect on acinar cells, enhancing basal glucagon secretion from isolated perfused rat pancreas, and potentiating glucose-stimulated insulin secretion in perfused rat islets and insulin-secreting clonal beta-cell lines, suggest that TRH may play a role in pancreas. TRH also enlarged pancreas and increased pancreatic DNA content but deletion of TRH gene expression caused hyperglycemia in mice, suggesting that TRH may play a critical role in pancreatic development; however, the biological mechanisms of TRH in the adult pancreas remains unclear.


OBJECTIVE
This study explored the effect of TRH on rat pancreas.


METHODS
Four male-Sprague-Dawley-rats (200-250 g) were given 10 microg/kg BW of TRH intraperitoneally on 1st and 3rd day and sacrificed on 7th day. Four same-strain rats without TRH injection served as controls.


METHODS
Wet pancreatic weights were measured. Pancreatic tissues were homogenized and extracted. The insulin levels of the extracts were measured by ELISA. Total RNA from the pancreases were fluorescently labeled and hybridized to microarray with 1,081 spot genes.


RESULTS
TRH increased pancreatic wet weight and insulin contents. About 75% of the 1,081 genes were detected in the pancreas. TRH regulated up 99 genes and down 76 genes. The administration of TRH induced various types of gene expressions, such as G-protein coupled receptors (GPCR) and signal transduction related genes (GPCR kinase 4, transducin beta subunit 5, arrestin beta1MAPK3, MAPK5, c-Src kinase, PKCs, PI3 kinase), growth factors (PDGF-B, IGF-2, IL-18, IGF-1, IL-2, IL-6, endothelin-1) and apoptotic factors (Bcl2, BAD, Bax).


CONCLUSIONS
Reprogramming of transcriptome may be a way for TRH-regulation of pancreatic cellular functions.
Yano
Naohiro
N
Hallett Center for Diabetes and Endocrinology, Rhode Island Hospital, Brown Medical School, Providence, RI 02903, USA.
Luo
LuGuang
L
D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D015536:Down-Regulation / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005796:Genes / Q000502:physiology; D007328:Insulin / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D009929:Organ Size; D010179:Pancreas / Q000737:chemistry* / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D012107:Research Design; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology / Q000502:physiology*; D014020:Tissue Extracts / Q000737:chemistry; D015854:Up-Regulation / Q000502:physiology
D007328:Insulin; D014020:Tissue Extracts; D013973:Thyrotropin-Releasing Hormone; D012313:RNA