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睾丸中硫酸化甾体激素的转运蛋白——表达模式、生物学意义及其对男性和啮齿动物生育能力的影响。

Transporter for sulfated steroid hormones in the testis - expression pattern, biological significance and implications for fertility in men and rodents.

机构信息

Institute for Veterinary Anatomy, Histology and Embryology, Justus Liebig University Giessen, Giessen, Germany.

出版信息

J Steroid Biochem Mol Biol. 2018 May;179:8-19. doi: 10.1016/j.jsbmb.2017.10.001. Epub 2017 Oct 7.

DOI:10.1016/j.jsbmb.2017.10.001
PMID:29017936
Abstract

In various tissues, steroid hormones may be sulfated, glucuronidated or otherwise modified. For a long time, these hydrophilic molecules have been considered to be merely inactive metabolites for excretion via bile or urine. Nevertheless, different organs such as the placenta and breast tissue produce large amounts of sulfated steroids. After the discovery of the enzyme steroid sulfatase, which is able to re-activate sulfated steroids, these precursor molecules entered the focus of interest again as a local supply for steroid hormone synthesis with a prolonged half-life compared to their unconjugated counterparts. The first descriptions of this so-called sulfatase pathway in the placenta and breast tissue (with special regards to hormone-dependent breast cancer) were quickly followed by studies of steroid sulfate production and function in the testis. These hydrophilic molecules may not permeate the cell membrane by diffusion in the way that unbound steroids can, but need to be transported through the plasma membrane by transport systems. In the testis, a functional sulfatase pathway requires the expression of specific uptake carrier and efflux transporters in testicular cells, i.e. Sertoli, Leydig and germ cells. Main focus has to be placed on Sertoli cells, as these cells build up the blood-testis barrier. In this review, an overview of carrier expression pattern in the human as well as rodent testis is provided with special interest towards implications on fertility.

摘要

在各种组织中,甾体激素可能会被硫酸化、葡萄糖醛酸化或以其他方式修饰。长期以来,这些亲水性分子被认为只是通过胆汁或尿液排泄的无活性代谢物。然而,不同的器官,如胎盘和乳腺组织,会产生大量的硫酸化甾体。类固醇硫酸酯酶的发现后,这种酶能够使硫酸化甾体重新激活,这些前体分子再次成为人们关注的焦点,因为它们作为甾体激素合成的局部供应,与未结合的甾体相比具有更长的半衰期。在胎盘和乳腺组织(特别是与激素依赖性乳腺癌有关)中首次描述了这种所谓的硫酸酯酶途径后,人们很快就开始研究睾丸中甾体硫酸酯的产生和功能。这些亲水性分子不能像未结合的甾体那样通过扩散穿过细胞膜,但需要通过转运系统穿过质膜进行运输。在睾丸中,功能性硫酸酯酶途径需要在睾丸细胞(即支持细胞、间质细胞和生殖细胞)中表达特定的摄取载体和外排转运体。研究的重点必须放在支持细胞上,因为这些细胞构建了血睾屏障。在这篇综述中,提供了人类和啮齿动物睾丸中载体表达模式的概述,并特别关注其对生育能力的影响。

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