steroids 71 ( 2 0 0 6 ) 653–659 available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/steroids Estrogen effects on thyroid iodide uptake and thyroperoxidase activity in normal and ovariectomized rats L´ ıvia P. Lima, Inˆ es A. Barros, Patr´ ıcia C. Lisb ˆ oa, Renata L. Ara ´ ujo, Alba C.M. Silva, Doris Rosenthal, Andrea C.F. Ferreira, Denise P. Carvalho ∗ Laborat ´ orio de Fisiologia End ´ ocrina, Instituto de Biof´ ısica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil article info Article history: Received 24 August 2005 Received in revised form 9 March 2006 Accepted 13 March 2006 Published on line 9 June 2006 Keywords: 17--Estradiol benzoate Ovariectomy Thyroid iodide uptake Thyroperoxidase abstract Sex steroids interfere with the pituitary–thyroid axis function, although the reports have been controversial and no conclusive data is available. Some previous reports indicate that estradiol might also regulate thyroid function through a direct action on the thyrocytes. In this report, we examined the effects of low and high doses of estradiol administered to control and ovariectomized adult female rats and to pre-pubertal females. We demon- strate that estradiol administration to both intact adult and pre-pubertal females causes a significant increase in the relative thyroid weight. Serum T3 is significantly decreased in ovariectomized rats, and is normalized by estrogen replacement. Neither doses of estrogen produced a significant change in serum TSH and total T4 in ovariectomized, adult intact and pre-pubertal rats. The highest, supraphysiological, estradiol dose produced a signifi- cant increase in thyroid iodide uptake in ovariectomized and in pre-pubertal rats, but not in control adult females. Thyroperoxidase activity was significantly higher in intact adult rats treated with both estradiol doses and in ovariectomized rats treated with the highest estradiol dose. Since serum TSH levels were not significantly changed, we suggest a direct action of estradiol on the thyroid gland, which depends on the age and on the previous gonad status of the animal. © 2006 Elsevier Inc. All rights reserved. 1. Introduction The prevalence of thyroid diseases is higher in women than in men, and in the postmenopausal period a further increase in the incidence of thyroid dysfunction is detected [1,2]. Estro- gen possibly stimulates thyrotrophin (TSH) secretion; however some previous reports indicate that this hormone might also regulate thyroid function through a direct action on thyrocytes [3–8]. The findings that the administration of estradiol stim- ∗ Corresponding author at: Instituto de Biof´ ısica Carlos Chagas Filho, UFRJ, CCS-Bloco G-Cidade Universit´ aria, Ilha do Fund ˜ ao, Rio de Janeiro, 21949-900, Brazil. Tel.: +55 21 25626552; fax: +55 21 22808193. E-mail address: dencarv@biof.ufrj.br (D.P. Carvalho). ulates thyroid radioiodine uptake in rats that were ovariec- tomized and hypophysectomized [9] support the hypothesis of a direct effect of estrogen on the thyroid. More recently, the presence of estrogen receptors has been demonstrated in both human and rat thyroid glands [10–12]. Moreover, estradiol increases the FRTL-5 rat thyroid cell line proliferation either in the presence or absence of TSH [3]. Estradiol also regulates thy- roid cell proliferation in vivo, since ovariectomy limits thyroid growth induced by low iodide diet, and sex steroids increase 0039-128X/$ – see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.steroids.2006.03.007