环境内分泌干扰物影响垂体促性腺激素的研究进展
Influences of Endocrine-disrupting Chemicals on Pituitary Gonadotropins: A Review
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摘要: 通过工业和农业生产活动排入环境的多种农药、阻燃剂、多氯联苯、塑料包装成分、防腐剂、工业副产物和重金属等化学物质，已被证明是内分泌干扰物(endocrine-disrupting chemicals, EDCs)，通过各种途径干扰内分泌系统，例如作用下丘脑-垂体-性腺(hypothalamic-pituitary-gonad, HPG)轴。垂体是HPG轴中联系下丘脑与性腺的重要内分泌器官，合成和分泌2种促性腺激素，即黄体生成素(luteinizing hormone, LH)和卵泡刺激素(follicle-stimulating hormone, FSH)，在调控性成熟与生殖发育过程中起到不可或缺的作用。如果垂体促性腺细胞作为EDCs作用的靶标，LH和FSH的合成、分泌、转运或者代谢受到干扰，可能会引起生殖系统的内分泌紊乱，影响性成熟和生殖功能，甚至增加生殖障碍等相关疾病风险。已有一些环境流行病学调查和动物实验报道EDCs暴露与人体及哺乳动物体内LH和FSH水平改变相关，但影响促性腺激素的作用机制研究却相对有限。本文对近年来EDCs影响促性腺激素的环境流行病学调查、动物实验以及毒理学机制研究的进展进行综述，并探讨未来的研究方向。Abstract: A variety of pesticides, flame retardants, polychlorinated biphenyls, chemical in plastic articles, preservatives, industrial by-products, heavy metals and other pollutants, which are discharged into the environment through industrial and agricultural activities, have been proven to be endocrine-disrupting chemicals (EDCs). Disruption of endocrine system by EDCs can occur in various ways, such as acting on the hypothalamic-pituitary-gonad (HPG) axis. The pituitary is an important endocrine organ in the HPG axis that connects the hypothalamus and the gonads. The gonadotropic cells in pituitary synthesize and secrete two gonadotropins, i.e. luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which play an essential role in sexual maturation and reproduction. When the gonadotropin cells act as the targets of EDCs, the synthesis, secretion, transportation or metabolism of LH and FSH may be disturbed, resulting in hormone imbalance, altering sexual maturity, impairing reproduction and even increasing the risk of endocrine and reproductive diseases. Some environmental epidemiological investigations and animal experiments have reported that EDCs exposure was associated with the changes in the serum levels of LH and FSH in humans and mammals. However, the studies on the toxicological mechanisms of EDCs affecting the synthesis and secretion of these two gonadotropins are relatively limited. This review aims to summarize the environmental epidemiological investigations, animal studies, and toxicological mechanisms regarding the effects of EDCs on gonadotropins, as well as discuss future research directions.
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