Shi Ting, Xu Lin-Lin, Chen Liang, He Jun, Wang Ye-Ke, Chen Feng, Chen Yang, Giesy John P, Wang Yu-Ting, Wu Qian-Hui, Xu Wen-Li, Chen Jun, Xie Ping
Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology (IHB), Chinese Academy of Sciences (CAS), Wuhan, 430072, China; University of Chinese Academy of Sciences (UCAS), Beijing, 100049, China.
Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology (IHB), Chinese Academy of Sciences (CAS), Wuhan, 430072, China; University of Chinese Academy of Sciences (UCAS), Beijing, 100049, China; Institute for Ecological Research and Pollution Control of Plateau Lakes, School of Ecology and Environmental Science, Yunnan University, Kunming, 650500, China.
Environ Pollut. 2023 Feb 1;318:120843. doi: 10.1016/j.envpol.2022.120843. Epub 2022 Dec 9.
Microcystins (MCs) produced by some cyanobacteria can cause toxicity in animals and humans. In recent years, growing evidence suggests that MCs can act as endocrine disruptors. This research systematically investigated effects of microcystin-LR (MC-LR) on endocrine organs, biosynthesis of hormones and positive/negative feedback of the endocrine system in rats. Male, Sprague-Dawley rats were acutely administrated MC-LR by a single intraperitoneal injection at doses of 45, 67.5 or 90 μg MC-LR/kg body mass (bm), and then euthanized 24 h after exposure. In exposed rats, histological damage of hypothalamus, pituitary, adrenal, testis and thyroid were observed. Serum concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT), expressions of genes and proteins for biosynthesis of hormones were lesser, which indicated an overall suppression of the hypothalamus-pituitary-adrenal (HPA) axis. Along the hypothalamus-pituitary-gonadal (HPG) axis, lesser concentrations of gonadotropin-releasing hormone (GnRH) and testosterone (T), but greater concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol (E2) were observed. Except for greater transcription of cyp19a1 in testes, transcriptions of genes and proteins for T and E2 biosynthesis along the HPG axis were lesser. As for the hypothalamus-pituitary-thyroid (HPT) axis, after MCs treatment, greater concentrations of thyroid-stimulating hormone (TSH), but lesser concentrations of free tri-iodothyronine (fT3) were observed in serum. Concentrations of free tetra-iodothyronine (fT4) were greater in rats dosed with 45 μg MCs/kg, bm, but lesser in rats dosed with 67.5 or 90 μg MCs/kg, bm. Transcripts of genes for biosynthesis of hormones and receptors along the HPT axis and expressions of proteins for biosynthesis of tetra-iodothyronine (T4) and tri-iodothyronine (T3) in thyroid were significantly altered. Cross-talk among the HPA, HPG and HPT axes probably occurred. It was concluded that MCs caused an imbalance of positive and negative feedback of hormonal regulatory axes, blocked biosynthesis of key hormones and exhibited endocrine-disrupting effects.
一些蓝藻产生的微囊藻毒素（MCs）可导致动物和人类中毒。近年来，越来越多的证据表明，MCs可作为内分泌干扰物。本研究系统地调查了微囊藻毒素-LR（MC-LR）对大鼠内分泌器官、激素生物合成以及内分泌系统正/负反馈的影响。将雄性Sprague-Dawley大鼠通过腹腔注射以45、67.5或90μg MC-LR/千克体重（bm）的剂量急性给予MC-LR，然后在暴露24小时后实施安乐死。在暴露的大鼠中，观察到下丘脑、垂体、肾上腺、睾丸和甲状腺的组织学损伤。促肾上腺皮质激素释放激素（CRH）、促肾上腺皮质激素（ACTH）和皮质酮（CORT）的血清浓度、激素生物合成相关基因和蛋白质的表达均降低，这表明下丘脑-垂体-肾上腺（HPA）轴受到全面抑制。沿着下丘脑-垂体-性腺（HPG）轴，观察到促性腺激素释放激素（GnRH）和睾酮（T）浓度降低，但黄体生成素（LH）、卵泡刺激素（FSH）和雌二醇（E2）浓度升高。除睾丸中cyp19a1转录增加外，HPG轴上T和E2生物合成相关基因和蛋白质的转录均降低。至于下丘脑-垂体-甲状腺（HPT）轴，MCs处理后，血清中促甲状腺激素（TSH）浓度升高，但游离三碘甲状腺原氨酸（fT3）浓度降低。在给予45μg MCs/kg bm的大鼠中，游离甲状腺素（fT4）浓度升高，但在给予67.5或90μg MCs/kg bm的大鼠中降低。HPT轴上激素和受体生物合成相关基因的转录以及甲状腺中甲状腺素（T4）和三碘甲状腺原氨酸（T3）生物合成相关蛋白质的表达均发生显著改变。HPA、HPG和HPT轴之间可能发生了相互作用。得出的结论是，MCs导致激素调节轴的正反馈和负反馈失衡，阻断关键激素的生物合成，并表现出内分泌干扰作用。
