Triiodothyronine indirectly increases amphiregulin gene expression levels via estrogen receptor activation

The objective of this study was to determine whether triiodothyronine hormone (T 3 ) exerts direct or indirect modulation in amphiregulin (AREG) gene expression. To elucidate the modulation type, MCF‐7 cells were treated with T3 (10 −8 M) for 60 minutes in the presence or absence of fulvestran (estrogen receptor inhibitor ‐ ICI) or cycloheximide (protein translation inhibitor – CHX). Gene expression was assessed by RT‐qPCR, considering statistical significance level at 5%. Treatment with T3 increased amphiregulin 1 gene expression (± 0.16, control group) to 13.93 (± 2.09, P <0.001). When treating cells with T 3 and ICI simultaneously, amphiregulin mRNA expression decreased to 9.74 (± 1.44, P <0.05) and when treating cells with T 3 and CHX, amphiregulin mRNA expression decreased to 0.88 (± 0.07, P <0.001). These results demonstrate that T 3 increases amphiregulin gene expression via estrogen receptor. The decrease in amphiregulin expression by CHX in the group treated with T3 demonstrates that such modulation occurs indirectly, i.e., there is a need of protein synthesis prior to gene modulation. Financial support: FAPESP: 2009/15607–2