Institute of Nutrition and Food Technology, INTA, University of Chile, Santiago, Chile.
Biol Trace Elem Res. 2010 Jun;134(3):252-64. doi: 10.1007/s12011-009-8475-x. Epub 2009 Aug 14.
Classic copper indicators are not sensitive and specific for detecting excess copper exposure when this is higher than customary but not markedly elevated. Serum copper and ceruloplasmin (Cp) are the most commonly used indicators to assess nutritional status of copper. The objective of this paper was to study the influence of estrogens on these indicators and others used to assess early effects of excess copper exposure in humans and the expression of a set of copper related proteins in a hepatic cellular model. For the studies in humans, 107 healthy participants (18-50 years) were allocated as follows: group 1 (n = 39), women assessed on day 7 of their hormonal cycle; group 2 (n = 34), women assessed on day 21 of their hormonal cycle, and group 3 (n = 34, comparison group), healthy men. Participants received 8 mg Cu/day (as copper sulfate) during 6 months. Serum Cp and Cu, Cu-Zn-superoxide dismutase activity, liver function indicators [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyltransferase (GGT)], and serum Fe and Zn concentrations were measured monthly. In addition, the influence of estradiol on intracellular total copper content, hctr1, dmt1 and shbg mRNA abundance and hCTR1, and DMT1 expression was measured in HepG2 cells. Serum Cu, Fe, and Zn and liver aminotransferases but not Cu-Zn-superoxide dismutase varied depending on sex. Fe nutrition indicators, GGT, and ALT activities showed significant differences between the hormonal phases. Cellular experiments showed that estradiol increased cellular Cu concentration and hCTR1 and DMT1 mRNA expression and changed these proteins expression patterns. Estradiols significantly influence the responses to copper at the whole body and the cellular levels, suggesting that they help maintaining copper availability for metabolic needs.
经典的铜指标在检测铜暴露过量时并不敏感和特异，尤其是当铜暴露量高于常规水平但并不明显升高时。血清铜和铜蓝蛋白（Cp）是评估铜营养状况最常用的指标。本文的目的是研究雌激素对这些指标以及其他用于评估人类铜暴露过量早期影响的指标的影响，以及在肝细胞模型中一组与铜相关的蛋白质的表达。在人类研究中，将 107 名健康参与者（18-50 岁）分为以下三组：第 1 组（n=39），女性在激素周期的第 7 天评估；第 2 组（n=34），女性在激素周期的第 21 天评估；第 3 组（n=34，对照组），健康男性。参与者在 6 个月内每天接受 8mgCu（以硫酸铜形式）。每月测量血清 Cp 和 Cu、Cu-Zn-超氧化物歧化酶活性、肝功能指标（天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）和γ-谷氨酰转移酶（GGT））以及血清 Fe 和 Zn 浓度。此外，还测量了雌激素对 HepG2 细胞内总铜含量、hctr1、dmt1 和 shbg mRNA 丰度以及 hCTR1 和 DMT1 表达的影响。血清 Cu、Fe 和 Zn 以及肝脏氨基转移酶的水平因性别而异。Fe 营养指标、GGT 和 ALT 活性在激素周期的不同阶段有显著差异。细胞实验表明，雌二醇增加了细胞内铜浓度和 hCTR1 和 DMT1 mRNA 的表达，并改变了这些蛋白质的表达模式。雌二醇对全身和细胞水平的铜反应有显著影响，表明它们有助于维持铜的代谢需求。
