Lambert F, Lammerant J, Kolanowski J
J Steroid Biochem. 1983 Jun;18(6):731-5. doi: 10.1016/0022-4731(83)90252-2.
The mechanism of the prolonged stimulatory effect of corticotropin (ACTH) on adrenocortical synthesis of cortisol was studied in guinea-pig adrenocortical cells harvested from control animals and from guinea-pigs submitted 24 h before the sacrifice to a prolonged ether anesthesia in an attempt to induce a release of endogenous ACTH. As a result of this in vivo exposure to endogenous ACTH, the maximal capacity to produce glucocorticoids (by 1 X 10(5) cells incubated during 2 h) in response to ACTH increased from 579 +/- 111 ng (control group) to 915 +/- 143 ng for cells from treated animals, whereas the apparent affinity of the steroidogenic response to ACTH remained unchanged. This hyper-reactivity of cells from anesthetized animals was also evident in the presence of dibutyryl cyclic AMP. Moreover, there was increased conversion of exogenous pregnenolone into cortisol by cells from previously anesthetized animals. It was therefore concluded that ACTH increases in a lasting way the activity of steroidogenic pathway leading to cortisol synthesis by adrenocortical cells at sites distal to cyclic AMP generation. Besides an obvious increase of formation of pregnenolone in response to ACTH, it seems that this ACTH-induced enhancement in the capacity of the steroidogenic response to ACTH also implies a prolonged stimulatory influence of the peptide on the post-pregnenolone steroidogenic pathway leading to cortisol synthesis.
研究了促肾上腺皮质激素(ACTH)对肾上腺皮质合成皮质醇的延长刺激作用机制,实验采用从对照动物以及在处死前24小时接受长时间乙醚麻醉以诱导内源性ACTH释放的豚鼠身上获取的肾上腺皮质细胞。由于这种体内暴露于内源性ACTH的情况,响应ACTH产生糖皮质激素的最大能力(通过1×10⁵个细胞培养2小时),对于来自处理动物的细胞,从对照组的579±111纳克增加到915±143纳克,而类固醇生成反应对ACTH的表观亲和力保持不变。在存在二丁酰环磷酸腺苷的情况下,麻醉动物细胞的这种高反应性也很明显。此外,来自先前麻醉动物的细胞对外源性孕烯醇酮转化为皮质醇的转化率增加。因此得出结论,ACTH以持久的方式增加了肾上腺皮质细胞在环磷酸腺苷生成位点远端导致皮质醇合成的类固醇生成途径的活性。除了响应ACTH时孕烯醇酮形成明显增加外,似乎这种ACTH诱导的类固醇生成反应能力增强也意味着该肽对导致皮质醇合成的孕烯醇酮后类固醇生成途径有延长的刺激影响。