Influence of Estrogens on Copper Indicators: In Vivo and In Vitro Studies |
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Authors: | Miguel Arredondo Héctor Núñez Guadalupe López Fernando Pizarro Mariana Ayala Magdalena Araya |
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Institution: | (1) Micronutrient Laboratory, Institute of Nutrition and Food Technology, INTA, University of Chile, Santiago, Chile;(2) INTA, University of Chile, Macul 5540, Santiago, 11, Chile; |
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Abstract: | 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. |
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