促阿片-黑素细胞皮质素原肽和血管紧张素II对分离的醛固酮瘤细胞类固醇生成的影响。

Pham-Huu-Trung M T, Bogyo A, de Smitter N, Girard F

J Clin Endocrinol Metab. 1985 Sep;61(3):467-71. doi: 10.1210/jcem-61-3-467.

Cells isolated from five aldosterone-producing adenomas were used to study glucocorticoid and aldosterone production in response to ACTH, angiotensin II (A II), and peptides derived from proopiomelanocortin (POMC), viz. the 16K N-terminal fragment (16K) and its derivative, gamma 3MSH and the C-terminal fragment beta-lipotropin (beta LPH) and its derivative beta-endorphin. At concentrations similar to those of ACTH and A II (10(-12)-10(-10) M), 16K, gamma 3MSH, and beta LPH selectively stimulated aldosterone production, which reached levels close to those obtained with A II. ACTH, however, was the most effective stimulant of steroidogenesis. The 16K, gamma 3MSH, and beta LPH peptides potentiated the action of ACTH, particularly in the case of aldosterone production. beta-Endorphin, whether used alone or in association with ACTH, had no effect on steroidogenesis at the dose used (10(-10) M). The principal glucocorticoid products of the adenoma cells were cortisol and corticosterone. The ratios of corticosterone to cortisol (B/F) and aldosterone to corticosterone (A/B) varied considerably from one adenoma to another, both basally and in response to ACTH. Nevertheless, within individual adenomas, the mean B/F ratio induced by ACTH [0.280 +/- 0.013 (+/- SEM)] was significantly larger than that induced by A II (0.127 +/- 0.007; P less than 0.001). By contrast, the A/B ratio in response to ACTH (0.061 +/- 0.003) was significantly smaller than that in response to A II (0.159 +/- 0.010; P less than 0.001). The values obtained with 16K (B/F, 0.106 +/- 0.010; A/B, 0.192 +/- 0.028) and gamma 3MSH (B/F, 0.122 +/- 0.012; A/B, 0.178 +/- 0.020) were close to those obtained with A II. 16K and gamma 3MSH potentiated ACTH's effect on steroidogenesis mainly by increasing the A/B ratio from 0.061 +/- 0.003 for ACTH alone to 0.100 +/- 0.008 for 16K plus ACTH (P less than 0.005) and to 0.092 +/- 0.005 for gamma 3MSH plus ACTH (P less than 0.001). The findings suggest that the stimulation of aldosterone production by 16K and gamma 3MSH in aldosteronoma cells is of the A II type and that these peptides may play a role in the genesis of primary aldosteronism.

从五个醛固酮分泌性腺瘤中分离出的细胞，用于研究糖皮质激素和醛固酮的产生，以响应促肾上腺皮质激素（ACTH）、血管紧张素II（A II）以及源自阿黑皮素原（POMC）的肽类，即16K N端片段（16K）及其衍生物γ3促黑素（γ3MSH）、C端片段β-促脂素（βLPH）及其衍生物β-内啡肽。在与ACTH和A II相似的浓度（10⁻¹² - 10⁻¹⁰ M）下，16K、γ3MSH和βLPH选择性地刺激醛固酮的产生，其水平接近A II所诱导的水平。然而，ACTH是类固醇生成最有效的刺激物。16K、γ3MSH和βLPH肽增强了ACTH的作用，特别是在醛固酮产生方面。β-内啡肽无论是单独使用还是与ACTH联合使用，在所使用的剂量（10⁻¹⁰ M）下对类固醇生成均无影响。腺瘤细胞的主要糖皮质激素产物是皮质醇和皮质酮。皮质酮与皮质醇的比率（B/F）以及醛固酮与皮质酮的比率（A/B）在不同腺瘤之间以及基础状态和对ACTH反应时均有很大差异。然而，在单个腺瘤内，ACTH诱导的平均B/F比率[0.280 ± 0.013（±标准误）]显著大于A II诱导的比率（0.127 ± 0.007；P < 0.001）。相比之下，ACTH诱导的A/B比率（0.061 ± 0.003）显著小于A II诱导的比率（0.159 ± 0.010；P < 0.001）。16K（B/F，0.106 ± 0.010；A/B，0.192 ± 0.028）和γ3MSH（B/F，0.122 ± 0.012；A/B，0.178 ± 0.020）所获得的值接近A II所获得的值。16K和γ3MSH增强ACTH对类固醇生成的作用主要是通过将A/B比率从单独ACTH时的0.061 ± 0.003增加到16K加ACTH时的0.100 ± 0.008（P < 0.005）以及γ3MSH加ACTH时的0.092 ± 0.005（P < 0.001）。这些发现表明，16K和γ3MSH对醛固酮瘤细胞中醛固酮产生的刺激是A II型的，并且这些肽可能在原发性醛固酮增多症的发生中起作用。