MOLECULAR BIOLOGY OF PITUITARY GLYCOPROTEIN AND HYPOTHALAMIC RELEASING HORMONES

人促甲状腺激素β基因仅在人的促甲状腺激素细胞中表达 受下丘脑激素调节的垂体前叶，周期 AMP和甲状腺激素。最近的研究表明，TRH 而环状AMP在很大程度上通过 特异性垂体因子PIT-1的磷酸化变化 结合到转录起始上游的区域。相比之下， 甲状腺激素通过与一种调节因子结合来调节其抑制作用 转录开始下游的第一个元素 未翻译的外显子。 我们还详细描述了位于-1/+6处的TGGGTCA基序 HTSH-β基因，与上游PIT-1共同介导 HTSH-β基因的位点、蛋白激酶C和A以及TRH的刺激 表情。我们还展示了与c-fos和c-jun相互作用的 这个下游位点调节T3对HTSH-β基因表达的抑制。 我们最近发现了其他重要的调控序列 HTSH-β基因表达。其中一个区域是脑垂体特异性的TATAAA 序列位于-25，这对基础表达和调节表达都是至关重要的。 其他区域包括上游两个位置的独特消音器区域 在发起人身上。这些区域包括OCT-1结合位点，并出现 作为核基质附着区。

The human TSH beta gene is expressed only in the thyrotrophs of the anterior pituitary where it is regulated by hypothalamic hormones, cyclic AMP as well as thyroid hormone. Recent studies have indicated that TRH and cyclic AMP mediate their transcriptional action in large part through changes in phosphorylation of the specific pituitary factor pit-1 which binds to a region upstream of the start of transcription. In contrast, thyroid hormone mediates its inhibition through binding to a regulatory element downstream of the start of transcription in the first untranslated exon. We have also characterized in detail a TGGGTCA motif at -1/+6 of the hTSH-beta gene that mediates, in conjunction with the upstream pit-1 site, protein kinase C and A as well as TRH stimulation of hTSH-beta gene expression. We have also shown that c-fos and c-jun which interact with this downstream site modulate T3 inhibition of hTSH-beta gene expression. We have recently recognized other important regulatory sequences for hTSH-beta gene expression. One such area is a pituitary-specific TATAAA sequence at -25 which is vital for both basal and regulated expression. Other regions include unique silencer regions at two locations upstream in the promoter. These regions include Oct-1 binding sites and appear to act as nuclear matrix attachment regions.