Katakami H, Downs T R, Frohman L A
J Clin Invest. 1986 May;77(5):1704-11. doi: 10.1172/JCI112490.
The effects of thyroidectomy (Tx) and thyroxine replacement (T4Rx) on pituitary growth hormone (GH) secretion and hypothalamic GH-releasing hormone (GRH) concentration were compared to define the mechanism of hypothyroid-associated GH deficiency. Thyroidectomized rats exhibited a complete loss of pulsatile GH secretion with extensive reduction in GRH responsiveness and pituitary GH content. Cultured pituitary cells from Tx rats exhibited reduced GRH sensitivity, maximal GH responsiveness, and intracellular cyclic AMP accumulation to GRH, while somatostatin (SRIF) suppressive effects on GH secretion were increased. Hypothalamic GRH content was also markedly reduced. T4Rx completely restored hypothalamic GRH content and spontaneous GH secretion despite only partial recovery of pituitary GH content, GRH and SRIF sensitivity, and intracellular cyclic AMP response to GRH. The results indicate multiple effects of hypothyroidism on GH secretion and suggest that a critical role of T4 in maintaining normal GH secretion, in addition to restoring GH synthesis, is related to its effect on hypothalamic GRH.
为明确甲状腺功能减退相关生长激素(GH)缺乏的机制,比较了甲状腺切除术(Tx)和甲状腺素替代治疗(T4Rx)对垂体GH分泌及下丘脑GH释放激素(GRH)浓度的影响。甲状腺切除的大鼠表现出脉冲式GH分泌完全丧失,GRH反应性和垂体GH含量大幅降低。来自Tx大鼠的培养垂体细胞对GRH的敏感性、最大GH反应性及细胞内环磷酸腺苷(cAMP)积累均降低,而生长抑素(SRIF)对GH分泌的抑制作用增强。下丘脑GRH含量也显著降低。尽管垂体GH含量、GRH和SRIF敏感性以及细胞内cAMP对GRH的反应仅部分恢复,但T4Rx完全恢复了下丘脑GRH含量和自发性GH分泌。结果表明甲状腺功能减退对GH分泌有多种影响,并提示T4在维持正常GH分泌中除恢复GH合成外的关键作用与其对下丘脑GRH的作用有关。