The further analysis of negative thyroid hormone receptor elements in the 3'-untranslated region of human growth hormone gene

Thyroid hormones have myriad effects on both metabolism and development, while working together with growth hormone. The expression of human growth hormone (hGH) is regulated by triiodothyronine (T3). It was reported that the occurrence of negative thyroid hormone receptor elements (nTREs) located 3' to the coding sequence of the human growth hormone (hGH) gene mediates T3-dependent negative regulation of reporter cassettes in transfected pituitary tumor GC cells (Zhang W, et al 1992). To clarify the detailed sequence of the nTREs of hGH gene, we eliminated the potential effect of the vector-associated AP-1-like sequences to regulate the expression of hGH gene, through the expression study using plasmid vector containing mutated or deleted AP-1-like sequences. We next performed mutational anaylsis of hGH 3'-UTR and demonstrated the existence of complex nTREs, composed of inverted palindrome and multiple direct repeats, located just downstream of stop codon to the major polyadenylation site (nts 2024-2109). The location of nTREs in hGH is very unique compared to the other known nTREs which are located close to their promoter and regulate gene expression at the starting level of transcription. Further investigation is necessary, but the mechanism of T3-dependent repression in hGH gene may be partially associated with regulatory processes related to the unique position of nTREs in 3'-UTR. Taken together, the study indicated that the hGH gene expression is regulated intricately by T3, and these results may contribute to understanding of the T3-dependent regulatory effects on various genes and regulating system for growth and development.