Hupart K H, DeFesi C R, Katz C P, Shapiro L E, Surks M I
Department of Medicine, Montefiore Medical Center, Bronx, New York.
Acta Endocrinol (Copenh). 1989 Dec;121(6):811-6. doi: 10.1530/acta.0.1210811.
Rats bearing the Walker 256 carcinoma have decreased pituitary nuclear T3 but normal pituitary TSH content and response to experimental hypothyroidism. To elucidate further the role of T3 receptor occupancy and biological response in the tumor-bearing rat model of nonthyroidal disease, we measured the concentration of T3 nuclear receptors, rTSH and rGH and beta-TSH mRNA and GH mRNA in the anterior pituitary of euthyroid rats bearing the Walker 256 carcinoma. The abundance of T3 nuclear receptors was decreased in tumor-bearing rats and was associated with a decrease in mRNA content for beta-TSH and GH. alpha-tubulin mRNA was decreased to a comparable degree. The pituitary content of rTSH and rGH was, however, the same as in control animals. Since tumor rats have normal regulation of TSH secretion by thyroid hormone, the present findings suggest that TSH secretion in T rats is maintained by a lower T3 nuclear receptor occupancy than in controls. The decrease in beta-TSH mRNA may precede a decrease in TSH synthesis and changes in pituitary TSH stores. Since the decrease in GH mRNA was comparable to the decrease in alpha-tubulin mRNA, it does not appear to be specifically related to decreased T3 nuclear receptor occupancy. We conclude that, in the tumor-bearing rat model of nonthyroidal disease, decreases in beta-TSH mRNA occur despite a decreased T3 receptor occupancy. Both thyroid-dependent and thyroid-independent factors may be involved in regulating beta-TSH mRNA.
携带Walker 256癌的大鼠垂体细胞核T3减少，但垂体促甲状腺激素（TSH）含量正常，且对实验性甲状腺功能减退有正常反应。为了进一步阐明T3受体占有率和生物学反应在非甲状腺疾病荷瘤大鼠模型中的作用，我们测量了甲状腺功能正常的携带Walker 256癌大鼠垂体前叶中T3核受体、重组TSH（rTSH）和重组生长激素（rGH）的浓度以及β-TSH mRNA和GH mRNA的水平。荷瘤大鼠的T3核受体丰度降低，且与β-TSH和GH的mRNA含量减少有关。α-微管蛋白mRNA也有类似程度的降低。然而，垂体中rTSH和rGH的含量与对照动物相同。由于荷瘤大鼠的TSH分泌受甲状腺激素的正常调节，目前的研究结果表明，与对照组相比，荷瘤大鼠TSH分泌的维持是通过较低的T3核受体占有率实现的。β-TSH mRNA的减少可能先于TSH合成的减少和垂体TSH储备的变化。由于GH mRNA的减少与α-微管蛋白mRNA的减少程度相当，因此它似乎与T3核受体占有率的降低没有特异性关系。我们得出结论，在非甲状腺疾病荷瘤大鼠模型中，尽管T3受体占有率降低，但β-TSH mRNA仍会减少。甲状腺依赖性和甲状腺非依赖性因素可能都参与了β-TSH mRNA的调节。
