Liu Tianbing, Bowen Richard L, Wilson Andrea C, Atwood Craig S
Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, United States.
Department of Pathology and Laboratory Medicine, University of Wisconsin Madison School of Medicine and Public Health, Madison, WI, United States.
Front Neurol. 2022 May 11;13:841822. doi: 10.3389/fneur.2022.841822. eCollection 2022.
Alterations in brain metal ion homeostasis have been reported with aging and are implicated in the pathogenesis of neurodegenerative diseases. To assess whether age-related changes in hypothalamic-pituitary-gonadal (HPG) hormones might be involved in modulating brain metal ion homeostasis, we treated 7.5-month intact, sham-ovariecomized and ovariectomized C57B6SJL mice with vehicle or leuprolide acetate (for 9-months) to differentiate between whether sex steroids or gonadotropins might modulate brain metal ion concentrations. Unlike other aging mammals, there was no increase in plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations following estropause in mice, suggesting there was sufficient residual production by the follicle depleted ovary, of sex steroids like estrogens and protein hormones like the inhibins, in order to suppress pituitary LH/FSH production. Castration on the other hand induced significant increases in circulating LH and FSH. Modulation of plasma sex steroid and gonadotropin levels did not significantly alter the concentrations of brain metals tested (Fe, Zn, Cu, Mn, Co, Ni, Al, Li), although there was a tendency for a decrease in all brain metals following ovariectomy (low estrogens and progesterone, high gonadotropins), a response that was reversed with leuprolide acetate treatment (low sex steroids, low gonadotropins). Brain Cu concentration was the only metal correlated with plasma LH (-0.37, = 30, < 0.05) and FSH (-0.42, = 29, < 0.01). This study demonstrates that sex hormones do not markedly alter brain metal ion homeostasis, unlike previously reported studies of circulating metal ion homeostasis. The role of gonadotropins in regulating metal ion homeostasis does however warrant further study.
据报道，随着年龄增长，脑内金属离子稳态会发生改变，这与神经退行性疾病的发病机制有关。为了评估下丘脑 - 垂体 - 性腺（HPG）激素的年龄相关变化是否可能参与调节脑内金属离子稳态，我们用赋形剂或醋酸亮丙瑞林（处理9个月）对7.5月龄完整、假去卵巢和去卵巢的C57B6SJL小鼠进行处理，以区分是性类固醇还是促性腺激素可能调节脑内金属离子浓度。与其他衰老哺乳动物不同，小鼠绝经后血浆促黄体生成素（LH）和促卵泡生成素（FSH）浓度并未升高，这表明卵泡耗竭的卵巢仍有足够的残余产量来分泌雌激素等性类固醇和抑制素等蛋白质激素，从而抑制垂体LH/FSH的分泌。另一方面，去势会导致循环中的LH和FSH显著增加。尽管去卵巢后（雌激素和孕酮水平低，促性腺激素水平高）所有脑内金属都有下降趋势，而醋酸亮丙瑞林治疗（性类固醇水平低，促性腺激素水平低）可逆转这种反应，但血浆性类固醇和促性腺激素水平的调节并未显著改变所检测的脑内金属（铁、锌、铜、锰、钴、镍、铝、锂）的浓度。脑铜浓度是唯一与血浆LH（-0.37，n = 30，P < 0.05）和FSH（-0.42，n = 29，P < 0.01）相关的金属。这项研究表明，与先前关于循环金属离子稳态的研究不同，性激素不会显著改变脑内金属离子稳态。然而，促性腺激素在调节金属离子稳态中的作用确实值得进一步研究。
