Hormonal Regulation of the Thyrotropin Releasing Hormone lpar;TRHrpar; Gene

摘要

Significant advances in understanding the function, distribution, and hormonal regulation of TRH gene expression have occurred since the cloning of the TRH gene. TRH gene expression is widespread in the CNS and peripheral sites but only TRH mRNA located in the paraventricular nucleus is under negative regulation by thyroid hormone. Molecular biological experiments using gene transfer of TRH promoter-reporter mini' genes reproduce the in vivo transcriptional repression by thyroid hormones. In vitro binding studies using the TRH promoter demonstrate binding sites for transcriptional trans-acting factors including thyroid hormone receptor, CREB, and c-jun. The divergent hormonal response of the TRH gene in the thyrotropic area of the hypo-thalamus compared to peripheral sites illustrate the importance in hormonal regulation of the distribution of cell-specific factors including nuclear hormone receptors and transcription factors.The TRH stimulation test has been replaced by second and third generation TSH assays in the diagnosis of hypothyroidism. The paradoxical response of some pituitary adenomas to exogenous TRH administration allows the use of the TRH test as a marker for these tumors. The studies demonstrating the widespread distribution and function of TRH have provided information that has led to the new and exciting field of the therapeutic use of TRH in a wide array of clinical disorders.