Genomic and promoter structure of the TRH gene. The murine, rat and human TRH genes are composed of three exons and two introns (A). The coding sequence for the precursor protein is present on exons 2 and 3. As depicted, the TRH promoter region precedes the transcription start site in exon 1. The proximal 250-bp sequences of the human, mouse and rat promoters are similar and share the indicated transcription factor binding sites. The location of the CREB binding site (Site 4) and sequences in human (H), mouse (M) and rat (R) are shown. (B, C) Hypothesized schematic representation of the interaction between PCREB and the thyroid hormone receptor at Site 4. (B) Illustrates that in the presence of abundant PCREB, there may be less availability for binding of the thyroid hormone receptor/T3 complex, hence, an increase in TRH gene transcription. When PCREB concentrations fall as shown in (C), increased binding of the thyroid hormone receptor/T3 complex reduces TRH gene transcription (From Fekete & Lechan (128) with permission)