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大鼠肾小球带功能与醛固酮合成

Glomerulosa function and aldosterone synthesis in the rat.

作者信息

Vinson G P

机构信息

School of Biological Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS, UK.

出版信息

Mol Cell Endocrinol. 2004 Mar 31;217(1-2):59-65. doi: 10.1016/j.mce.2003.10.010.

Abstract

Since its discovery, it has been generally assumed that the primary function of the zona glomerulosa of the adrenal cortex is the secretion of aldosterone. Taking evidence from the rat, and recognising that there is probably considerable species variation, I argue here that the glomerulosa in fact has many functions, including aldosterone synthesis, but is probably only a relatively poor de novo source of steroid. In vitro, the CYP11B2 (aldosterone synthase) of the glomerulosa can and does utilise as substrates products arising from CYP11B1 (11beta-hydroxylase) activity in fasciculata cells. Whether it does in vivo is open to question, but corticosterone and 18-hydroxydeoxycorticosterone are both present in circulating rat plasma at suitable concentrations. Such a mechanism would explain several inconsistencies in the literature, including the anomalous distribution of steroidogenic enzymes in the glomerulosa, the stimulation of CYP11B1 products by aldosterone secretagogues such as potassium ions or angiotensin II, the partial dependence of aldosterone secretion in vivo on an intact pituitary, the sensitivity of aldosterone secretion to tissue disruption in vitro, and the "late pathway" regulation of aldosterone synthesis.

摘要

自发现以来,人们普遍认为肾上腺皮质球状带的主要功能是分泌醛固酮。基于大鼠的证据,并认识到可能存在相当大的物种差异,我在此认为,球状带实际上具有多种功能,包括醛固酮合成,但可能只是类固醇相对较差的从头合成来源。在体外,球状带的CYP11B2(醛固酮合酶)能够且确实利用束状带细胞中CYP11B1(11β-羟化酶)活性产生的产物作为底物。它在体内是否如此尚不确定,但皮质酮和18-羟脱氧皮质酮在循环大鼠血浆中均以合适的浓度存在。这样一种机制可以解释文献中的几个不一致之处,包括球状带中类固醇生成酶的异常分布、醛固酮分泌刺激剂(如钾离子或血管紧张素II)对CYP11B1产物的刺激、体内醛固酮分泌对完整垂体的部分依赖性、体外醛固酮分泌对组织破坏的敏感性以及醛固酮合成的“晚期途径”调节。

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