Molloy E S, Clarke D M, Fearon U M, Cunningham S K, McKenna T J
Department of Endocrinology and Diabetes Mellitus, St. Vincent's Hospital, Elm Park, Dublin, Ireland.
Steroids. 1998 Sep;63(9):459-63. doi: 10.1016/s0039-128x(98)00048-8.
The possibility that non-ACTH proopiomelanocortin-derived fragments may stimulate aldosterone production has previously been studied using nonhuman cells with inconsistent results. We have examined the response of aldosterone to beta-endorphin (beta-End) and joining peptide (JP) and compared these with the response to ACTH using eight cell suspensions prepared from human adrenal glands. ACTH, 10(-6), 10(-8), and 10(-10) M, consistently stimulated aldosterone accumulation above that occurring in unstimulated cells (150 +/- 83, 120 +/- 62, and 77 +/- 32 fmol/10(4) cells above basal, respectively; mean +/- SE; p < 0.05). beta-End significantly stimulated aldosterone production at 10(-6) and 10(-8) M (114 +/- 84 and 50 +/- 24 fmol/10(4) cells above basal; p < 0.05); 10(-10) M beta-End did not provide significant stimulation. Furthermore, JP stimulated aldosterone biosynthesis (41 +/- 16 fmol/10(4) cells above basal; p < 0.05), only at the highest concentration used, 10(-6) M. The addition of 10(-8) M ACTH plus 10(-6) and 10(-10) M beta-End to human adrenal cells yielded values significantly greater than those achieved with either agent alone (267 +/- 152 and 183 +/- 89 fmol/10(4) cells above basal; p < 0.05). These data indicate for the first time that beta-End and JP have the capacity to stimulate aldosterone production in human adrenal cells in vitro. The physiological and potential clinical significance of these observations has yet to be elucidated.
非促肾上腺皮质激素原阿黑皮素衍生片段可能刺激醛固酮生成，此前已使用非人类细胞对此可能性进行了研究，但结果并不一致。我们使用从人类肾上腺制备的八种细胞悬液，检测了醛固酮对β-内啡肽（β-End）和连接肽（JP）的反应，并将这些反应与对促肾上腺皮质激素（ACTH）的反应进行了比较。10⁻⁶、10⁻⁸和10⁻¹⁰M的ACTH持续刺激醛固酮积累，使其高于未刺激细胞中的积累量（分别比基础值高150±83、120±62和77±32 fmol/10⁴细胞；均值±标准误；p<0.05）。10⁻⁶和10⁻⁸M的β-End显著刺激醛固酮生成（分别比基础值高114±84和50±24 fmol/10⁴细胞；p<0.05）；10⁻¹⁰M的β-End未提供显著刺激。此外，JP仅在使用的最高浓度10⁻⁶M时刺激醛固酮生物合成（比基础值高41±16 fmol/10⁴细胞；p<0.05）。向人类肾上腺细胞中添加10⁻⁸M的ACTH以及10⁻⁶和10⁻¹⁰M的β-End，产生的值显著高于单独使用任何一种试剂时的值（分别比基础值高267±152和183±89 fmol/10⁴细胞；p<0.05）。这些数据首次表明，β-End和JP在体外具有刺激人类肾上腺细胞生成醛固酮的能力。这些观察结果的生理和潜在临床意义尚待阐明。
