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激素印迹的生物学基础及其临床意义:一种表观遗传过程。

The biological basis and clinical significance of hormonal imprinting, an epigenetic process.

机构信息

Department of Genetics, Cell and Immunobiology, Semmelweis University, 1445 Budapest, P.O. Box 370, Hungary.

出版信息

Clin Epigenetics. 2011 Aug;2(2):187-96. doi: 10.1007/s13148-011-0024-8. Epub 2011 Mar 1.

Abstract

The biological phenomenon, hormonal imprinting, was named and defined by us (Biol Rev, 1980, 55, 47-63) 30 years ago, after many experimental works and observations. Later, similar phenomena were also named to epigenetic imprinting or metabolic imprinting. In the case of hormonal imprinting, the first encounter between a hormone and its developing target cell receptor-usually at the perinatal period-determines the normal receptor-hormone connection for life. However, in this period, molecules similar to the target hormone (members of the same hormone family, synthetic drugs, environmental pollutants, etc), which are also able to bind to the receptor, provoke faulty imprinting also with lifelong-receptorial, behavioral, etc.,-consequences. Faulty hormonal imprinting could also be provoked later in life in continuously dividing cells and in the brain. Faulty hormonal imprinting is a disturbance of gene methylation pattern, which is epigenenetically inherited to the further generations (transgenerational imprinting). The absence of the normal or the presence of false hormonal imprinting predispose to or manifested in different diseases (e.g., malignant tumors, metabolic syndrome) long after the time of imprinting or in the progenies.

摘要

30 年前,我们(生物评论,1980 年,55 卷,47-63 页)在进行了大量实验和观察之后,命名并定义了这一生物学现象——激素印记。后来,类似的现象也被命名为表观遗传印记或代谢印记。在激素印记的情况下,激素与其发育中的靶细胞受体的首次相遇——通常在围产期——决定了其一生中正常的受体-激素连接。然而,在此期间,与靶激素相似的分子(同一家族的成员、合成药物、环境污染物等),也能够与受体结合,引发错误的印记,从而导致终生的受体、行为等方面的后果。错误的激素印记也可能在不断分裂的细胞和大脑中在生命后期引发。错误的激素印记是基因甲基化模式的紊乱,这种紊乱会通过表观遗传传递给后代(跨代印记)。正常激素印记的缺失或错误激素印记的存在,会导致印记发生后很长一段时间或在后代中出现不同的疾病(例如恶性肿瘤、代谢综合征)。

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