Castro M, Moreira A C
Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brasil.
Braz J Med Biol Res. 1996 Nov;29(11):1573-8.
This study was undertaken to determine the short-loop negative feedback at the hypothalamic site after adrenalectomy (ADX), when the hypothalamic-pituitary axis was a different set-points. Rats were submitted to the experimental procedure 3 h and 1, 3 and 14 days after bilateral ADX or sham surgery under ether anesthesia by the dorsal approach. ADX rats were supplied with 1.5% NaCl. After decapitation, plasma samples were collected and corticosterone (B) and adrenocorticotrophic hormone (ACTH) concentrations were determined by radioimmunoassay (RIA). Using in vitro incubation of the median basal hypothalamus (MBH) fragment we studied the hypothalamic corticotrophin-releasing hormone (CRH) release under basal conditions and under the inhibitory effect of ACTH. Hypothalamic CRH secretion, determined by direct RIA, without extraction and reported as pg CRH/MBH per 1 h incubation, was inhibited by ACTH administration in a dose-dependent manner, as demonstrated by a significant negative correlation obtained by linear regression analysis of CRH secretion as a function of ACTH dose. However, the percentage of inhibition of CRH secretion was higher at 1 and 3 days than at 14 days after ADX. In conclusion, these in vitro studies demonstrated that ACTH suppressed basal CRH secretion in a dose-dependent manner, an effect compatible with a short-loop feedback mechanism. Furthermore, we demonstrated variable suppressibility of CRH secretion by ACTH at different times after ADX.
本研究旨在确定肾上腺切除术后(ADX),当下丘脑 - 垂体轴处于不同设定点时,下丘脑部位的短环负反馈情况。在乙醚麻醉下,通过背部入路对大鼠进行双侧肾上腺切除术或假手术后3小时、1天、3天和14天进行实验操作。给肾上腺切除大鼠供应1.5%的氯化钠。断头后,采集血浆样本,通过放射免疫分析法(RIA)测定皮质酮(B)和促肾上腺皮质激素(ACTH)浓度。利用下丘脑正中基底部(MBH)片段的体外孵育,我们研究了基础条件下以及ACTH抑制作用下下丘脑促肾上腺皮质激素释放激素(CRH)的释放。通过直接RIA测定下丘脑CRH分泌,无需提取,以每1小时孵育pg CRH/MBH表示,结果显示ACTH给药以剂量依赖性方式抑制CRH分泌,这通过对CRH分泌作为ACTH剂量函数进行线性回归分析得到的显著负相关得以证明。然而,肾上腺切除术后1天和3天CRH分泌的抑制百分比高于14天。总之,这些体外研究表明,ACTH以剂量依赖性方式抑制基础CRH分泌,这一效应与短环反馈机制相符。此外,我们证明了肾上腺切除术后不同时间ACTH对CRH分泌的抑制作用存在差异。