Eggens U, Bähr V, Oelkers W, Li C H
Medizinische Klinik und Poliklinik, Abteilung Endokrinologie, Klinikum Steglitz, Freien Universität Berlin.
J Clin Chem Clin Biochem. 1987 Nov;25(11):779-83. doi: 10.1515/cclm.1987.25.11.779.
Normal human adrenocortical cells (from multi-organ donors) were incubated with corticotropin (tetracosactide), highly purified human beta-lipotropin, synthetic human beta-lipotropin, gamma 2-melanocyte stimulating hormone and beta-endorphin. Corticotropin stimulated cortisol, aldosterone and 18-hydroxycorticosterone production starting at 10(-12)-10(-11) mol/l in normal adrenocortical cells. Purified human beta-lipotropin also stimulated steroidogenesis but 100-1000-fold higher concentrations of the peptide were needed. In contrast, synthetic human beta-lipotropin was without any effect on steroid production up to concentrations of 10(-7) mol/l. Synthetic beta-lipotropin (5 x 10(-10) mol/l) did not significantly change the dose-response curve for corticotropin (10(-13) mol/l-10(-9) mol/l) versus the three steroids measured. gamma 2-Melanotropin and beta-endorphin (10(-6) mol/l) stimulated the secretion of cortisol, but not of aldosterone. Since synthetic human beta-lipotropin has no effect on human adrenocortical cells, the purified beta-lipotropin must be contaminated with traces of corticotropin. Since pathologically elevated levels of proopiomelanocortin-derived peptides will rarely exceed plasma concentrations of 10(-10) mol/l, our findings in vitro do not support a physiological or pathophysiological role of the peptides examined in the regulation of adrenal steroid secretion.
将正常人肾上腺皮质细胞(来自多器官供体)与促肾上腺皮质激素(二十四肽促皮质素)、高度纯化的人β-促脂解素、合成人β-促脂解素、γ2-黑素细胞刺激素和β-内啡肽一起孵育。促肾上腺皮质激素在正常人肾上腺皮质细胞中从10(-12)-10(-11)mol/L开始刺激皮质醇、醛固酮和18-羟皮质酮的产生。纯化的人β-促脂解素也刺激类固醇生成,但需要该肽浓度高100-1000倍。相比之下,合成人β-促脂解素在浓度高达10(-7)mol/L时对类固醇产生没有任何影响。合成β-促脂解素(5×10(-10)mol/L)与所测的三种类固醇相比,并没有显著改变促肾上腺皮质激素(10(-13)mol/L-10(-9)mol/L)的剂量反应曲线。γ2-促黑素和β-内啡肽(10(-6)mol/L)刺激皮质醇的分泌,但不刺激醛固酮的分泌。由于合成人β-促脂解素对人肾上腺皮质细胞没有影响,纯化的β-促脂解素必定被痕量的促肾上腺皮质激素污染。由于源自阿片促黑激素皮质素原的肽在病理状态下升高的水平很少会超过10(-10)mol/L的血浆浓度,我们的体外研究结果不支持所检测的这些肽在调节肾上腺类固醇分泌中具有生理或病理生理作用。