Lam K S, Wong R L
Department of Medicine, University of Hong Kong, Hong Kong, China.
Neuroendocrinology. 1999 Jun;69(6):460-4. doi: 10.1159/000054450.
Circulating TSH levels are increased in hypothyroidism and suppressed in hyperthyroidism. On the other hand, the hypothalamic hormone somatostatin suppresses basal and TRH-induced TSH release, an effect which is enhanced by thyroid hormones. To investigate whether the effects of thyroid hormones on TSH secretion may be mediated in part through alterations in the gene expression of pituitary somatostatin receptors (SSTR), 3-week-old male Sprague-Dawley rats were rendered hypothyroid with antithyroid drugs for 3 weeks. Total RNA extracted from anterior pituitaries were analysed for SSTR mRNA levels, using Northern blot hybridization. Compared to controls, hypothyroid rats had significantly lower pituitary mRNA levels of SSTR1 and SSTR2 (p < 0.0001 for both, n = 16); the reductions could be prevented by T4 supplementation (3 microgram/100 g body weight/day i.p.). In vitro studies using GH4C1 rat pituitary cells showed that the addition of T3 10(-8) M to cells cultured in charcoal-stripped bovine calf serum resulted in significant increases in mRNA levels of SSTR1 (p < 0.0001; n = 7) and the two transcripts of SSTR2 (p < 0.0005; n = 7). The increase for SSTR1 showed no further increase with higher doses of T3, but was time-dependent and could be seen consistently after 8 h of incubation. We conclude that thyroid hormones regulate the gene expression of SSTR subtypes in the pituitary, via a direct action on anterior pituitary cells. Changes in SSTR gene expression may contribute to the increase in circulating TSH levels in hypothyroidism.
甲状腺功能减退时循环中的促甲状腺激素（TSH）水平升高，而甲状腺功能亢进时则受到抑制。另一方面，下丘脑激素生长抑素可抑制基础状态下及促甲状腺激素释放激素（TRH）诱导的TSH释放，甲状腺激素可增强这一作用。为研究甲状腺激素对TSH分泌的影响是否部分通过垂体生长抑素受体（SSTR）基因表达的改变介导，将3周龄雄性Sprague-Dawley大鼠用抗甲状腺药物诱导甲状腺功能减退3周。采用Northern印迹杂交分析从垂体前叶提取的总RNA中SSTR mRNA水平。与对照组相比，甲状腺功能减退大鼠垂体中SSTR1和SSTR2的mRNA水平显著降低（两者p<0.0001，n = 16）；补充T4（3微克/100克体重/天，腹腔注射）可预防这种降低。使用GH4C1大鼠垂体细胞的体外研究表明，在经活性炭处理的小牛血清中培养的细胞中加入10(-8) M的T3，可导致SSTR1的mRNA水平显著升高（p<0.0001；n = 7）以及SSTR2的两种转录本水平显著升高（p<0.0005；n = 7）。SSTR1的升高在更高剂量的T3作用下未进一步增加，但具有时间依赖性，在孵育8小时后可始终观察到。我们得出结论，甲状腺激素通过对垂体前叶细胞的直接作用调节垂体中SSTR亚型的基因表达。SSTR基因表达的变化可能导致甲状腺功能减退时循环TSH水平升高。
