Expression of thyrotropin-releasing hormone (TRH) receptor subtype 1 in mouse pancreatic islets and HIT-T15, an insulin-secreting clonal beta cell line

Thyrotropin-releasing hormone (TRH), originally isolated as a hypothalamic hormone, has been reported to be present and released from the pancreatic b eta cells, affecting pancreatic functions. However, it still remains unclea r whether TRH receptor is expressed in the pancreas. In the present study, we characterized TRH receptors (TRHR) in mouse pancreatic islets and HIT-T1 5 cells, a hamster clonal beta cell line. RT-PCR study showed significant e xpression of TRHR subtype 1 (TRHR1) mRNA in both mouse pancreatic islets an d HIT-T15 (HIT) cells. In contrast, there was no expression of TRHR2 mRNA, a novel subtype of TRHR which is expressed predominantly in the central ner vous system. Sequencing analysis demonstrated that TRHR1 of the islets was identical to that in the pituitary, and cloned hamster TRHR1 shared 93.3 % homology with that of the mouse at the nucleic acid level. Northern blot an alysis of TRHR1 mRNA in HIT-T15 cells showed a single strong hybridization signal approximately 3.7 kb in length. Furthermore, Scatchard plot analysis in HIT-T15 cells revealed that the Kd value for MeTRH was 0.63 nM. Signifi cant elevation of intracellular calcium concentration was observed in respo nse to as little as 10 nM TRH, and this was not affected by removal of extr acellular calcium. This is the first description indicating the presence of functional TRH receptor subtype 1 in the pancreatic beta cells, and our ob servations suggested the regulation of pancreatic function by TRH through a utocrine or paracrine mechanisms.