Ono M, Harigai T, Furudate S
Department of Molecular Biology, Kitasato University, Kanagawa, Japan.
J Endocrinol. 1994 Dec;143(3):479-87. doi: 10.1677/joe.0.1430479.
The pituitary gland of the rdw rat (gene symbol: rdw) with hereditary dwarfism expresses 30-100 times less GH and prolactin (PRL) mRNA than normal controls. To clarify the features of rdw rats, TSH and the pituitary-specific transcription factor Pit-1, which is involved not only in the gene expression of GH and PRL but in somatotroph, lactotroph and thyrotroph development as well, were examined. The rdw pituitary contained about seven times more TSH beta mRNA than the normal control, whereas Pit-1 mRNA expression in rdw and control was the same. Nucleotide sequencing of PCR-amplified Pit-1 cDNA indicated that the deduced amino acid sequence of rdw Pit-1 was identical with that of the normal rat. Using an antibody against rat Pit-1 protein produced in E. coli, Western blotting analysis demonstrated the presence of the same amount of Pit-1 protein in rdw and normal rat pituitaries. The distribution of Pit-1-positive cells in the anterior pituitary was essentially the same in rdw and normal rats. It follows from these findings that the defective gene in the rdw rat is unrelated to the Pit-1 gene and the normal quantity of Pit-1 protein is insufficient to produce normal amounts of GH and PRL in the rdw pituitary. These and previous results suggest that the reduction in GH and PRL production in the rdw pituitary might be due to that in thyroid hormone production.
患有遗传性侏儒症的rdw大鼠（基因符号：rdw）的垂体所表达的生长激素（GH）和催乳素（PRL）mRNA比正常对照少30至100倍。为了阐明rdw大鼠的特征，对促甲状腺激素（TSH）和垂体特异性转录因子Pit-1进行了检测，Pit-1不仅参与GH和PRL的基因表达，还参与生长激素细胞、催乳激素细胞和促甲状腺激素细胞的发育。rdw大鼠的垂体中TSHβmRNA含量比正常对照多约7倍，而rdw大鼠和对照大鼠中Pit-1 mRNA的表达相同。对PCR扩增的Pit-1 cDNA进行核苷酸测序表明，rdw大鼠Pit-1推导的氨基酸序列与正常大鼠相同。使用针对大肠杆菌产生的大鼠Pit-1蛋白的抗体，蛋白质免疫印迹分析表明rdw大鼠和正常大鼠垂体中Pit-1蛋白的含量相同。rdw大鼠和正常大鼠垂体前叶中Pit-1阳性细胞的分布基本相同。从这些发现可以推断，rdw大鼠中的缺陷基因与Pit-1基因无关，并且正常数量的Pit-1蛋白不足以在rdw大鼠的垂体中产生正常量的GH和PRL。这些结果以及之前的结果表明，rdw大鼠垂体中GH和PRL产生减少可能是由于甲状腺激素产生减少所致。
