Quinnipiac University Frank H. Netter MD School of Medicine, Hamden, CT, United States.
National Institute of Environmental Health Sciences, National Institutes of Health, Durham, NC, United States.
Adv Pharmacol. 2021;92:191-235. doi: 10.1016/bs.apha.2021.04.001. Epub 2021 May 3.
Sex-steroid receptors (SSRs) are essential mediators of estrogen, progestin, and androgen signaling that are critical in vast aspects of human development and multi-organ homeostasis. Dysregulation of SSR function has been implicated in numerous pathologies including cancers, obesity, Type II diabetes mellitus, neuroendocrine disorders, cardiovascular disease, hyperlipidemia, male and female infertility, and other reproductive disorders. Endocrine disrupting chemicals (EDCs) modulate SSR function in a wide variety of cell and tissues. There exists strong experimental, clinical, and epidemiological evidence that engagement of EDCs with SSRs may disrupt endogenous hormone signaling leading to physiological abnormalities that may manifest in disease. In this chapter, we discuss the molecular mechanisms by which EDCs interact with estrogen, progestin, and androgen receptors and alter SSR functions in target cells. In addition, the pathological consequences of disruption of SSR action in reproductive and other organs by EDCs is described with an emphasis on underlying mechanisms of receptors dysfunction.
性激素受体（SSR）是雌激素、孕激素和雄激素信号转导的重要介质，在人类发育和多器官稳态的各个方面都起着至关重要的作用。SSR 功能失调与许多疾病有关，包括癌症、肥胖、2 型糖尿病、神经内分泌紊乱、心血管疾病、高脂血症、男性和女性不孕以及其他生殖障碍。内分泌干扰化学品（EDC）可调节多种细胞和组织中的 SSR 功能。有强有力的实验、临床和流行病学证据表明，EDC 与 SSR 的结合可能会破坏内源性激素信号转导，导致可能表现为疾病的生理异常。在本章中，我们讨论了 EDC 与雌激素、孕激素和雄激素受体相互作用并改变靶细胞中 SSR 功能的分子机制。此外，还描述了 EDC 破坏 SSR 在生殖和其他器官中的作用所带来的病理后果，并重点介绍了受体功能障碍的潜在机制。
