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成年狨猴肾上腺皮质网状带的可塑性:新世界的探索之旅

Plasticity of the zona reticularis in the adult marmoset adrenal cortex: voyages of discovery in the New World.

作者信息

Pattison J Christina, Abbott David H, Saltzman Wendy, Conley Alan J, Bird Ian M

机构信息

Perinatal Research Laboratories, University of Wisconsin-Madison, 7E Meriter Hospital/Park, 202 South Park Street, Madison, Wisconsin 53715, USA.

出版信息

J Endocrinol. 2009 Dec;203(3):313-26. doi: 10.1677/JOE-08-0554. Epub 2009 May 27.

Abstract

Adrenarche in humans occurs at the age of 5-7 years, yet the process by which dehydroepiandrosterone (DHEA) biosynthesis in the adrenal zona reticularis (ZR) increases so dramatically remains as a matter of debate. One suggestion is that increased DHEA production by P450c17 (CYP17A1 as listed in HUGO Database) in the ZR results from a coincident fall in the expression of HSD3B, which would otherwise compete for pregnenolone substrate. Nonetheless, studies of human and rhesus adrenal show that cytochrome b5 (CYTB5) expression increases in the ZR with DHEA biosynthesis, and cloned human and rhesus P450c17 show selective increases in 17,20-lyase activity in the presence of CYTB5. The marmoset, a New World primate, expresses a fetal zone during development which regresses after birth. Adult males, however, do not develop an obvious functional ZR, while females develop a ZR in a manner that depends on their social/gonadal status. In all social and physiologic states, changes in marmoset ZR function relate directly to changes in the expression of CYTB5. Recent cloning and expression of marmoset P450c17 also show that while amino acid sequence homology is in the order of approximately 85% of that found in human and rhesus sequences, and basal lyase activity is low compared with rhesus, all previously described amino acids critical to human 17,20-lyase activity are completely conserved. Furthermore, the 17,20-lyase activity of the marmoset P450c17 clone is dramatically increased by addition of CYTB5. We propose that these combined data from the marmoset model provide further compelling evidence that the control of ZR CYTB5 expression is a key determinant of ZR function.

摘要

人类肾上腺功能初现发生在5至7岁,但肾上腺网状带(ZR)中脱氢表雄酮(DHEA)生物合成如此显著增加的过程仍存在争议。一种观点认为,ZR中P450c17(HUGO数据库中列为CYP17A1)产生的DHEA增加是由于HSD3B表达同时下降,否则HSD3B会竞争孕烯醇酮底物。然而,对人类和恒河猴肾上腺的研究表明,随着DHEA生物合成,ZR中细胞色素b5(CYTB5)的表达增加,并且克隆的人类和恒河猴P450c17在有CYTB5存在时17,20-裂解酶活性有选择性增加。狨猴是一种新大陆灵长类动物,在发育过程中会表达一个胎儿带,出生后会退化。然而,成年雄性不会发育出明显的功能性ZR,而雌性则根据其社会/性腺状态以一种方式发育出ZR。在所有社会和生理状态下,狨猴ZR功能的变化都与CYTB5表达的变化直接相关。最近对狨猴P450c17的克隆和表达也表明,虽然氨基酸序列同源性约为人类和恒河猴序列的85%,并且与恒河猴相比基础裂解酶活性较低,但所有先前描述的对人类17,20-裂解酶活性至关重要的氨基酸都是完全保守的。此外,添加CYTB5后,狨猴P450c17克隆的17,20-裂解酶活性显著增加。我们认为,来自狨猴模型的这些综合数据提供了进一步令人信服的证据,即ZR中CYTB5表达的控制是ZR功能的关键决定因素。

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