Elias A N, Vaziri N D, Pandian M R, Iyer K, Ansari M A
Nephron. 1987;46(3):301-4. doi: 10.1159/000184371.
The role of gamma-aminobutyric acid (GABA) in the abnormal secretion of thyrotropic hormone (TSH) in uremia was studied in male Sprague-Dawley rats rendered renally insufficient by subtotal nephrectomy. Baseline TSH concentrations in normal control animals and in the uremic animals were similar. The peak TSH response to thyrotropin-releasing hormone (TRH; 5 micrograms i.v.) was significantly blunted in the uremic animals compared to the controls. Pretreatment of the uremic animals with the specific GABA antagonist, bicuculline (1.5 mumol i.v.) resulted in normalization of the peak TSH response to TRH. Bicuculline pretreatment, however, did not alter the basal secretion of TSH in either the normal or the uremic animals, and it also did not augment the TRH-stimulated TSH response in the normal animals. Sham-operated animals demonstrated basal and TRH-stimulated TSH responses comparable to the control group. In order to assess whether the weight loss associated with uremia could have accounted for the blunted TRH-stimulated TSH secretion in the uremic animals, a group of rats were starved so that their weights were comparable to those of the uremic animals. Basal and TRH-stimulated TSH responses in this group were not significantly different from the controls. Bicuculline pretreatment of the starved animals also failed to alter the basal and TRH-stimulated TSH responses. These data indicate that an increase in central gabaergic tone may be partly responsible for the blunted TSH response to TRH seen in uremia, but that GABA is not an important modulator of TSH secretion in the normal rat.
在通过次全肾切除术导致肾功能不全的雄性Sprague-Dawley大鼠中，研究了γ-氨基丁酸（GABA）在尿毒症促甲状腺激素（TSH）异常分泌中的作用。正常对照动物和尿毒症动物的基础TSH浓度相似。与对照组相比，尿毒症动物对促甲状腺激素释放激素（TRH；静脉注射5微克）的TSH峰值反应明显减弱。用特异性GABA拮抗剂荷包牡丹碱（静脉注射1.5微摩尔）预处理尿毒症动物，可使对TRH的TSH峰值反应恢复正常。然而，荷包牡丹碱预处理并未改变正常或尿毒症动物的TSH基础分泌，也未增强正常动物中TRH刺激的TSH反应。假手术动物的基础和TRH刺激的TSH反应与对照组相当。为了评估与尿毒症相关的体重减轻是否可以解释尿毒症动物中TRH刺激的TSH分泌减弱，一组大鼠被禁食，使其体重与尿毒症动物相当。该组的基础和TRH刺激的TSH反应与对照组无显著差异。对饥饿动物进行荷包牡丹碱预处理也未能改变基础和TRH刺激的TSH反应。这些数据表明，中枢GABA能张力增加可能部分导致了尿毒症中TSH对TRH反应减弱，但GABA不是正常大鼠中TSH分泌的重要调节因子。
