Duox expression and related H2O2 measurement in mouse thyroid: Onset in embryonic development and regulation by TSH in adult

Abstract

In the thyroid, H2O2 is produced at the apical pole of thyrocytes by one or two NADPH oxidases (NOX), Duox1/2 proteins. The onset of Duox expression was analysed by immunohistochemistry in the developing mouse thyroid in parallel with thyroglobulin (Tg) iodination and the expression of other thyroid differentiation markers. Duox proteins were found at embryonic day (E) 15.5 and were mainly localised at the apical pole of thyrocytes. Tg was detected 1 day before (E14.5) and Tg iodination was concomitant with the expression of both Duox and Na+/I- symporter (NIS; E15.5). The role of TSH in regulating Duox expression and H2O2 accumulation was evaluated in thyroids of adult mice with reduced (Tshrhyt/hyt or mice treated with thyroxine) or increased (methimazole or perchlorate treatment) TSH/Tshr activity. In mice with suppressed TSH/Tshr activity, Duox expression was only partially decreased when compared with wild-type, as observed by western blot. In Tshrhyt/hyt strain, Duox was still expressed at the apical pole and H2O2 measurements were normal. On the other hand, chronic TSH stimulation of the gland led to a decrease of H2O2 measurements without affecting Duox expression. The onset of Duox protein expression is compatible with their proposed function in thyroid hormone synthesis and it can be considered as a functional marker of the developing thyroid. However, Duox expression in adult is much less regulated by TSH than NIS and thyroperoxidase. It is not always correlated with the overall thyroid H2O2 accumulation, highlighting the importance of additional regulatory mechanisms which control either the production or H2O2 degradation. © 2007 Society for Endocrinology.