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视黄酸与小鼠肾上腺中的醇/视黄醇脱氢酶:发育过程中视黄酸的潜在内分泌来源。

Retinoic acid and alcohol/retinol dehydrogenase in the mouse adrenal gland: a potential endocrine source of retinoic acid during development.

作者信息

Haselbeck R J, Ang H L, Deltour L, Duester G

机构信息

The Burnham Institute, La Jolla, California 92037, USA.

出版信息

Endocrinology. 1997 Jul;138(7):3035-41. doi: 10.1210/endo.138.7.5274.

DOI:10.1210/endo.138.7.5274
PMID:9202249
Abstract

Retinoid signaling requires the conversion of retinol to retinoic acid by a two-step process, the first of which can be catalyzed in vitro by class I and class IV alcohol dehydrogenases (ADH). These enzymes may participate in local retinoic acid synthesis in some target tissues, although other studies suggest retinoic acid may also be supplied to tissues via the bloodstream, much like an endocrine hormone. Here we have analyzed the expression of these two ADHs as well as retinoic acid production in the adrenal gland, an organ known to be an endocrine source of other hormones. In situ hybridization revealed high levels of both class I and class IV ADH messenger RNAs in adrenal glands of 16.5-day mouse embryos and adults. Class I ADH protein was immunohistochemically detected in embryonic and adult adrenal glands, the latter primarily in the zona fasiculata of the cortex. Abundant class IV ADH protein was detected in the embryonic adrenal as well as in the zona glomerulosa and zona fasiculata of the adult adrenal cortex. Interestingly, class IV ADH protein was found in only a subset of adult cortical cells arranged in radial columns, thus providing further evidence for centripetal cell migration during adrenocortical differentiation. Using a retinoic acid bioassay, adrenal glands from 16.5 day embryos were found to have significantly higher levels of retinoic acid than embryonic liver. The adult adrenal was found to have approximately 15.5 pmol/g of retinoic acid, whereas the adult liver had 24.8 pmol/g, and brain, heart, and spleen each had less than 1.0 pmol/g. Because previous findings indicate that the adrenal gland is not a retinoid target tissue, our detection of both alcohol/retinol dehydrogenases and significant amounts of retinoic acid in this organ suggests that it functions as a potential endocrine source of this hormone during mouse development.

摘要

维甲酸信号传导需要通过两步过程将视黄醇转化为视黄酸,其中第一步在体外可由I类和IV类醇脱氢酶(ADH)催化。这些酶可能参与某些靶组织中的局部视黄酸合成,尽管其他研究表明视黄酸也可能通过血液循环供应到组织中,这很像一种内分泌激素。在这里,我们分析了这两种ADH的表达以及肾上腺中视黄酸的产生,肾上腺是已知的其他激素的内分泌来源器官。原位杂交显示,在16.5天的小鼠胚胎和成年小鼠的肾上腺中,I类和IV类ADH信使核糖核酸水平都很高。I类ADH蛋白在胚胎和成年肾上腺中通过免疫组织化学检测到,后者主要在皮质的束状带中。在胚胎肾上腺以及成年肾上腺皮质的球状带和束状带中检测到大量的IV类ADH蛋白。有趣的是,IV类ADH蛋白仅在成年皮质细胞的一个子集中被发现,这些细胞排列成放射状柱,从而为肾上腺皮质分化过程中的向心细胞迁移提供了进一步的证据。使用视黄酸生物测定法,发现16.5天胚胎的肾上腺中视黄酸水平明显高于胚胎肝脏。发现成年肾上腺中视黄酸含量约为15.5 pmol/g,而成年肝脏为24.8 pmol/g,脑、心脏和脾脏的视黄酸含量均低于1.0 pmol/g。由于先前的研究结果表明肾上腺不是维甲酸靶组织,我们在该器官中检测到醇/视黄醇脱氢酶和大量视黄酸,这表明在小鼠发育过程中,肾上腺作为这种激素的潜在内分泌来源发挥作用。

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