Downs T R, Chomczynski P, Frohman L A
Department of Internal Medicine, University of Cincinnati College of Medicine, Ohio 45267.
Mol Endocrinol. 1990 Mar;4(3):402-8. doi: 10.1210/mend-4-3-402.
The role of thyroid hormone and GH in the regulation of hypothalamic GH-releasing hormone (GRH) gene expression in the rat was examined after the induction of thyroid hormone deficiency by thyroidectomy. Thyroidectomy resulted in a time-dependent decrease in hypothalamic GRH content, which was significant by 2 weeks postoperatively, and a reduction in pituitary GH content to 1% of the control level by 4 weeks. In contrast, GRH secretion by incubated hypothalami under both basal and K(+)-stimulated conditions was increased after thyroidectomy. Hypothalamic GRH mRNA levels also exhibited a time-dependent increase, which was significant at 1 week and maximal by 2 weeks after thyroidectomy. Administration of antirat GH serum to thyroidectomized rats resulted in a further increase in GRH mRNA levels. T4 treatment of thyroidectomized rats for 5 days, which also partially restored pituitary GH content, lowered the elevated GRH mRNA levels. However, comparable effects on GRH mRNA levels were observed by rat GH treatment alone. These results suggest that the changes in hypothalamic GRH gene expression after thyroidectomy in the rat are due to the GH deficiency caused by thyroidectomy, rather than a direct effect of thyroid hormone on the hypothalamus, since the changes were reversible by GH alone despite persistent thyroid hormone deficiency. In addition, they further support the role of GH as a physiological negative feedback regulator of GRH gene expression.
通过甲状腺切除诱导大鼠甲状腺激素缺乏后，研究了甲状腺激素和生长激素（GH）在调节大鼠下丘脑生长激素释放激素（GRH）基因表达中的作用。甲状腺切除导致下丘脑GRH含量随时间下降，术后2周时显著下降，垂体GH含量在4周时降至对照水平的1%。相反，甲状腺切除后，在基础和K⁺刺激条件下孵育的下丘脑GRH分泌增加。下丘脑GRH mRNA水平也呈现出随时间的增加，在甲状腺切除后1周时显著增加，2周时达到最大值。给甲状腺切除的大鼠注射抗大鼠GH血清导致GRH mRNA水平进一步升高。对甲状腺切除的大鼠进行5天的T4治疗，这也部分恢复了垂体GH含量，降低了升高的GRH mRNA水平。然而，单独用大鼠GH治疗也观察到了对GRH mRNA水平的类似影响。这些结果表明，大鼠甲状腺切除后下丘脑GRH基因表达的变化是由于甲状腺切除引起的GH缺乏，而不是甲状腺激素对下丘脑的直接作用，因为尽管甲状腺激素持续缺乏，但单独用GH就能使这些变化逆转。此外，它们进一步支持了GH作为GRH基因表达的生理负反馈调节因子的作用。
