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关于男性化肾上腺皮质腺瘤中甾体激素代谢的研究。

Studies on the metabolism of steroid hormones in a virilizing adrenal cortex adenoma.

作者信息

Lisboa B P, Strassner M, Nocke-Finck L, Breuer H, Bayer J M

出版信息

Endokrinologie. 1978 Nov;72(3):311-26.

PMID:217678
Abstract

Slices of an adreno-cortical adenoma which had been obtained at operation from an 11-year-old girl with clinical signs of virilism were incubated with each of the following steroids: [1,2-3H]progesterone, [4-14C]pregnenolone, [1,2-3H]testosterone, [4-14C]androstenedione and [7-3H]dehydroepiandrosterone, respectively. Isolation and identification of the free radioactive metabolites were achieved by gel column chromatography on Sephadex LH-20, thin-layer chromatography, radio gas chromatography and isotope dilution. After incubation of progesterone, the following metabolites were identified: 11beta-hydroxyprogesterone, 16alpha-hydroxyprogesterone, 17alpha-hydroxyprogesterone, 21-deoxycortisol, corticosterone and cortisol. Pregnenolone was metabolized to 17alpha-hydroxypregnenolone, progesterone, dehydroepiandrosterone, androstenedione and 11beta-hydroxyandrostenedione. When testosterone was used as substrate, 11beta-hydroxytestosterone, androstenedione and 11beta-hydroxyandrostenedione were found as metabolites, whereas androstenedione was metabolized to testosterone and 11beta-hydroxyandrostenedione. After incubation of dehydroepiandrosterone, only androstenedione and 11beta-hydroxyandrostenedione were isolated and identified. From these results, it appears that cortisol was formed in the adenoma tissue via 21-deoxycortisol and corticosterone. Delta4-3oxo steroids of the C19-series arose exclusively from pregnenolone via 17alpha-hydroxypregnenolone and dehydroepiandrosterone, and not from progesterone and 17alpha-hydroxyprogesterone. Calculated on the amounts of metabolites formed, the highest enzyme activities were those of the 11beta-hydroxylase and the 17alpha-hydroxylase. It is interesting to note that only traces of testosterone were detected after incubation of androstenedione, whereas testosterone yielded large amounts of androstenedione.

摘要

从一名患有男性化临床体征的11岁女孩手术中获取的肾上腺皮质腺瘤切片,分别与以下每种类固醇一起孵育:[1,2-³H]孕酮、[4-¹⁴C]孕烯醇酮、[1,2-³H]睾酮、[4-¹⁴C]雄烯二酮和[7-³H]脱氢表雄酮。通过在Sephadex LH-20上进行凝胶柱色谱、薄层色谱、放射性气相色谱和同位素稀释来实现游离放射性代谢物的分离和鉴定。孕酮孵育后,鉴定出以下代谢物:11β-羟基孕酮、16α-羟基孕酮、17α-羟基孕酮、21-脱氧皮质醇、皮质酮和皮质醇。孕烯醇酮代谢为17α-羟基孕烯醇酮、孕酮、脱氢表雄酮、雄烯二酮和11β-羟基雄烯二酮。当以睾酮为底物时,发现11β-羟基睾酮、雄烯二酮和11β-羟基雄烯二酮为代谢物,而雄烯二酮代谢为睾酮和11β-羟基雄烯二酮。脱氢表雄酮孵育后,仅分离并鉴定出雄烯二酮和11β-羟基雄烯二酮。从这些结果来看,似乎皮质醇是通过21-脱氧皮质醇和皮质酮在腺瘤组织中形成的。C19系列的Δ⁴-3氧代类固醇仅通过17α-羟基孕烯醇酮和脱氢表雄酮从孕烯醇酮产生,而非来自孕酮和17α-羟基孕酮。根据形成的代谢物量计算,最高的酶活性是11β-羟化酶和17α-羟化酶的活性。有趣的是,雄烯二酮孵育后仅检测到微量睾酮,而睾酮则产生大量雄烯二酮。

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Steroid biochemistry of virilising adrenal tumours in childhood.儿童期男性化肾上腺肿瘤的类固醇生物化学
Eur J Pediatr. 1984 Aug;142(3):165-9. doi: 10.1007/BF00442442.