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甲吡酮在不同昼夜节律阶段对小鼠肾上腺类固醇合成的体外作用。

The in vitro effect of metyrapone on steroid synthesis in mice adrenals at different circadian stages.

作者信息

Touitou Y, Bogdan A, Auzéby A, Lévi F

机构信息

Department of Biochemistry, Faculté de Médecine Pitié-Salpêtrière, Paris, France.

出版信息

Chronobiol Int. 1992 Oct;9(5):350-5. doi: 10.3109/07420529209064546.

Abstract

The circadian rhythm of the in vitro biosynthesis of cortisol and cortisone in mice adrenals has been documented in the absence and presence of 0.1 mumol metyrapone, an inhibitor of steroid 11 beta-monooxygenase. After 3 weeks of synchronization with 12 h light:12 h darkness, adrenalectomy was performed at eight circadian stages: 0, 4, 9, 10, 13, 16, 21, and 22 h after light onset (HALO). Because it has been shown that mice adrenals could convert exogenous 11-deoxycortisol, the synthesis of 11-oxysteroids (cortisol+cortisone) in adrenal homogenates was studied from tritiated precursor. The pattern of steroid synthesis showed a maximum around the end (10 HALO) and a minimum at the beginning of the resting period (0 HALO); the variation was approximately 10%. A similar pattern was observed in the presence of a approximately 50% inhibiting dose of metyrapone. On the other hand, the percent inhibition of 11-oxysteroids synthesis was greater at the beginning of the resting period (0 HALO) and minimum around the end of the activity span (21 HALO), with an overall variation of 20%. However, the variations were statistically insignificant (unpaired t test).

摘要

在不存在和存在0.1微摩尔美替拉酮(一种类固醇11β-单加氧酶抑制剂)的情况下,已记录了小鼠肾上腺中皮质醇和可的松体外生物合成的昼夜节律。在与12小时光照:12小时黑暗同步3周后,在八个昼夜节律阶段进行肾上腺切除术:光照开始后0、4、9、10、13、16、21和22小时(HALO)。由于已表明小鼠肾上腺可转化外源性11-脱氧皮质醇,因此从氚标记的前体研究了肾上腺匀浆中11-氧代类固醇(皮质醇+可的松)的合成。类固醇合成模式在静止期开始时(0 HALO)最低,在静止期结束时(10 HALO)左右最高;变化约为10%。在存在约50%抑制剂量的美替拉酮的情况下观察到类似模式。另一方面,11-氧代类固醇合成的抑制百分比在静止期开始时(0 HALO)更大,在活动期结束时(21 HALO)左右最小,总体变化为20%。然而,这些变化在统计学上无显著意义(未配对t检验)。

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