Insulin-like factor 3 as a monitor of endocrine disruption
Insulin-like factor 3 as a monitor of endocrine disruption
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DOI：
10.1530/rep-13-0486
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发表时间：
2014-04-01
期刊：
影响因子：
3.8
通讯作者：
Ivell, Richard
中科院分区：
文献类型：
--
作者：
Anand-Ivell, Ravinder;Ivell, Richard
胰岛素样因子3(INSL3)是由分化的间质细胞产生和分泌的，在所有哺乳动物物种中，胎儿和成年雄性都是如此。到目前为止的所有证据表明，它的产生是结构性的，独立于下丘脑-垂体-性腺轴(HPG)的急性调节，其数量反映了间质细胞的数量和分化状态。这种间质细胞的功能能力只能由雄激素输出来监控，然而，这在很大程度上受到HPG轴的剧烈调节和其他导致实质性和不规则短期变化的因素的干扰。在男性胎儿和成人的睾丸发育不全综合征中，间质细胞是内分泌干扰剂的主要靶点。在男性胎儿中，INSL3负责睾丸下降的第一阶段，因此与隐睾症的病因直接相关。在这项研究中，通过测量INSL3的产生，例如，在胎儿生命期间通过羊水，或作为胎儿睾丸外植体的分泌物，或在成人外周血中，我们和其他人已经表明INSL3是评估内分泌干扰剂的影响及其作用机制的一个有用的定量和敏感的终点。
Insulin-like factor 3 (INSL3) is generated and secreted by differentiated interstitial Leydig cells of the testes in both fetal and adult males of all mammalian species so far analyzed. All evidence to date suggests that it is produced constitutively, independently of acute regulation by the hypothalamo-pituitary-gonadal (HPG) axis, in amounts which reflect the numbers and differentiation status of the Leydig cells. This Leydig cell functional capacity is otherwise monitored only by androgen output, which, however, is massively confounded by acute regulation from the HPG axis and other factors leading to substantial and irregular short-term variation. Leydig cells are a primary target of endocrine-disrupting agents in the context of the testicular dysgenesis syndrome in the fetal male, as well as in the adult. In the male fetus, INSL3 is responsible for the first phase of testicular descent, and hence is directly linked to the etiology of cryptorchidism. In this study, by measuring INSL3 production, for example, during fetal life via amniotic fluid, or as secretions from fetal testis explants, or in adult peripheral blood, we and others have shown that INSL3 represents a useful quantitative and sensitive endpoint for assessing the impact of endocrine-disrupting agents and their mechanisms of action.