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雄性狨猴在出生时具有肾上腺胎儿带,但成年后没有网状带。

Male marmoset monkeys express an adrenal fetal zone at birth, but not a zona reticularis in adulthood.

作者信息

Pattison J Christina, Abbott David H, Saltzman Wendy, Nguyen Ann D, Henderson Gary, Jing Hongwu, Pryce Christopher R, Allen Amy J, Conley Alan J, Bird Ian M

机构信息

Perinatal Research Laboratories, University of Wisconsin-Madison, Madison, Wisconsin 53715, USA.

出版信息

Endocrinology. 2005 Jan;146(1):365-74. doi: 10.1210/en.2004-0689. Epub 2004 Sep 30.

Abstract

Neonatal human males produce high levels of dehydroepiandrosterone (DHEA) and its sulfo-conjugated form (DS) that decline within a few months of birth, due to regression of the adrenal fetal zone (FZ). Adult male humans and rhesus monkeys produce C19 steroids in abundance from the adrenal zona reticularis (ZR). Male marmoset monkeys produce DS at birth, but unlike humans and rhesus monkeys, do not produce comparable amounts of DHEA and DS in adulthood. To determine whether male marmosets express a functional ZR in adulthood, we examined adult and neonatal male marmosets for the presence of a ZR and FZ, respectively. Exogenous ACTH failed to stimulate DHEA or DS in adults, and dexamethasone treatment failed to suppress DHEA and DS, although cortisol levels changed as expected. In steroidogenic tissues, the key proteins necessary to synthesize C19 steroids from pregnenolone are P450c17, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), nicotinamide adenine dinucleotide phosphate (reduced) oxido-reductase cytochrome P450 (reductase), and cytochromeb5 (cytb5). Adult adrenal cross sections showed P450c17 and reductase protein expression throughout the cortex but showed no expected decrease in 3beta-HSD and increase in cytb5 in the innermost region. Western analysis confirmed these data, demonstrating comparable P450c17 expression to rhesus monkeys, but not cytb5. HPLC analysis revealed similar 17alpha-hydroxylase action on pregnenolone for adult marmoset and rhesus adrenal microsomes but greatly diminished 17,20-lyase activity in marmosets. Neonatal marmoset adrenals exhibited staining indicative of a putative FZ (with P450c17, reduced 3beta-HSD and increased cytb5). We conclude that neonatal marmosets exhibit a C19 steroid-secreting FZ similar to humans, but adult males fail to acquire a functional ZR.

摘要

新生的人类男性会产生高水平的脱氢表雄酮(DHEA)及其硫酸共轭形式(DS),但由于肾上腺胎儿带(FZ)的退化,这些物质在出生后的几个月内会下降。成年男性人类和恒河猴从肾上腺网状带(ZR)大量产生C19类固醇。雄性狨猴在出生时会产生DS,但与人类和恒河猴不同的是,成年后不会产生等量的DHEA和DS。为了确定成年雄性狨猴是否表达功能性的ZR,我们分别检查了成年和新生雄性狨猴是否存在ZR和FZ。外源性促肾上腺皮质激素(ACTH)未能刺激成年狨猴产生DHEA或DS,地塞米松治疗也未能抑制DHEA和DS,尽管皮质醇水平如预期那样发生了变化。在类固醇生成组织中,从孕烯醇酮合成C19类固醇所需的关键蛋白质是P450c17、3β - 羟基类固醇脱氢酶(3β - HSD)、烟酰胺腺嘌呤二核苷酸磷酸(还原型)氧化还原酶细胞色素P450(还原酶)和细胞色素b5(cytb5)。成年肾上腺切片显示P450c17和还原酶蛋白在整个皮质中表达,但在最内层区域未显示出预期的3β - HSD减少和cytb5增加。蛋白质免疫印迹分析证实了这些数据,表明P450c17的表达与恒河猴相当,但cytb5的表达并非如此。高效液相色谱分析显示,成年狨猴和恒河猴肾上腺微粒体对孕烯醇酮的17α - 羟化酶作用相似,但狨猴的17,20 - 裂解酶活性大大降低。新生狨猴肾上腺表现出的染色表明存在一个假定的FZ(具有P450c17、降低的3β - HSD和增加的cytb5)。我们得出结论,新生狨猴表现出与人类相似的分泌C19类固醇的FZ,但成年雄性狨猴未能获得功能性的ZR。

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