D'Angelo S A, Paul D H, Wall N R, Lombardi D M
Endocrinology. 1976 Oct;99(4):935-43. doi: 10.1210/endo-99-4-935.
The protein metabolism and [3H]-uridine uptake of thyroid and adenohypophysis and the kinetics of pituitary TSH rebound (PTR) were studied in goitrous female rats (fed propylthiouracil, PTU: for 7-12 weeks) following single, iv injections of L-thyroxine (T4: 0.8 to 200 mug). Goitrogenesis was associated with reduced protein concentration and enhanced uptake of [3H] uridine in both glands. Plasma levels of TSH were invariably elevated but stores in the adenohypophysis were consistently reduced. Small doses of T4 (4 mug) induced significant TSH repletion in the pituitary within 2-6 h following injection. Accumulations of pituitary TSH to supranormal levels (15-fold increases) were achieved with 20 mug T4 at 6 and 24 h; higher doses (100-200 mug) inhibited the PTR at all time intervals tested (0.5-24 h). Administration of puromycin or actinomycin D did not influence the PTR. Protein content and labeled uridine uptake of the pituitary bore no apparent relationship to T4-induced TSH repletion in the gland. Blood clearance rate of exogenous rat TSH was measured prior to and during PTR. Plasma half-life was determined to be 13.6 and 19.9 min in euthyroid and chronically hypothyroid rats, respectively; it was not significantly altered from the latter during rebound (18.7 min). Calculations of theoretical TSH secretory rates prior to (50.5 +/- 4.4 mU/h) and after rebound with 20 mug T4 (25.4 +/- 4.2 mU/H) revealed that the reaccumulation of TSH in the pituitary induced with T4 cannot be attributed solely to inhibition of release, but may also involve enhancement of synthesis. It is concluded that T4 administration at high dose levels inhibits both synthesis and release of TSH from pituitary thyrotrophs, whereas low critical doses of T4 suppress release, but augment synthesis and/or facilitate conformational change in a pituitary precursor(s) molecule which renders it detectable by bioassay.
对患甲状腺肿的雌性大鼠（喂食丙硫氧嘧啶，PTU：7 - 12周）单次静脉注射L - 甲状腺素（T4：0.8至200微克）后，研究了甲状腺和腺垂体的蛋白质代谢、[3H] - 尿苷摄取以及垂体促甲状腺激素反弹（PTR）的动力学。甲状腺肿的形成与两个腺体中蛋白质浓度降低和[3H]尿苷摄取增加有关。促甲状腺激素的血浆水平总是升高，但腺垂体中的储存量持续减少。小剂量的T4（4微克）在注射后2 - 6小时内可使垂体中的促甲状腺激素显著补充。在6小时和24小时时，20微克T4可使垂体促甲状腺激素积累至超正常水平（增加15倍）；更高剂量（100 - 200微克）在所有测试的时间间隔（0.5 - 24小时）均抑制PTR。给予嘌呤霉素或放线菌素D不影响PTR。垂体的蛋白质含量和标记尿苷摄取与T4诱导的腺体内促甲状腺激素补充无明显关系。在PTR之前和期间测量了外源性大鼠促甲状腺激素的血液清除率。在甲状腺功能正常和慢性甲状腺功能减退的大鼠中，血浆半衰期分别测定为13.6分钟和19.9分钟；在反弹期间（18.7分钟）与后者相比无显著变化。计算T4反弹前（50.5±4.4 mU/h）和20微克T4反弹后（25.4±4.2 mU/H）的理论促甲状腺激素分泌率表明，T4诱导的垂体中促甲状腺激素的重新积累不能仅归因于释放的抑制，还可能涉及合成的增强。结论是，高剂量的T4给药抑制垂体促甲状腺细胞中促甲状腺激素的合成和释放，而低临界剂量的T4抑制释放，但增加合成和/或促进垂体前体分子的构象变化，使其可通过生物测定法检测到。
