Anand-Ivell Ravinder, Ivell Richard
School of Biosciences, University of Nottingham, Sutton Bonington, UK.
Reproduction. 2014 Mar 2;147(4):R87-95. doi: 10.1530/REP-13-0486. Print 2014.
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.
胰岛素样因子3（INSL3）由所有已分析的哺乳动物物种的胎儿和成年雄性睾丸中分化的间质Leydig细胞产生并分泌。迄今为止的所有证据表明，它是组成性产生的，独立于下丘脑-垂体-性腺（HPG）轴的急性调节，其产生量反映了Leydig细胞的数量和分化状态。否则，Leydig细胞的这种功能能力只能通过雄激素输出进行监测，然而，雄激素输出会受到HPG轴的急性调节和其他因素的严重干扰，导致大量且不规则的短期变化。在胎儿期男性以及成年男性的睾丸发育不全综合征背景下，Leydig细胞是内分泌干扰物的主要靶标。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。在本研究中，例如通过测量胎儿期羊水、胎儿睾丸外植体分泌物或成年外周血中的INSL3产生量，我们和其他人已经表明，INSL3是评估内分泌干扰物影响及其作用机制的有用的定量和敏感终点。
