Abstract Leptin and thyroid hormones (TH) have the ability to increase energy expenditure. Biological effects of TH are dependent on thyroxine (T4) to triiodothyronine (T3) conversion by deiodinase type 1 (D1) and type 2 (D2). Leptin has been shown to stimulate the hypothalamus-pituitary-thyroid axis and, also, to modulate 5 0 -deiodinases in different tissues, depending on energetic status of animals. Here, we examined the acute effects of leptin on hypothalamic, pituitary and BAT D2 and pituitary D1 activities. Male fed rats received a single subcutaneous injection of saline or leptin (8 mg/100g BW) and sacrificed 2 hours later. Leptin promoted an important decrease in hypothalamic D2 (55 % reduction, p < 0.001) with no changes in pituitary D2, in con- comitance with a 2-fold rise in serum TSH, suggesting that leptin acted at hypothalamus in order to stimulate TRH-TSH axis. In addition, BAT D2 was decreased by 25 % (p < 0.05). In contrast, pituitary D1 showed a 2-fold increase (p < 0.001), indicating that, as demonstrated before for liver and thyroid D1, the pituitary enzyme is also acutely up-regulated by leptin. Serum concentra- tions of insulin and TH of leptin-injected animals remained unchanged. Regulation of 5 0 -deiodinases directing the local T3 production, is a mechanism by which leptin may alter hypotha- lamic, pituitary and BAT functions. Key words Thyrotropin Á thyroid hormones Á insulin Á thyrotropin-releasing hormone Introduction Leptin, an adipocyte-derived hormone, has a major role in reg- ulation of body weight, signaling energy sufficiency [1] and resistance to the anorectic action of leptin has been associated with nutritional disorders in adulthood or neonatal life leading to obesity [1–3]. Leptin and thyroid hormones share the ability to increase energy expenditure and thermogenesis [1, 4–6]. Bio- logical effects of thyroid hormones depend, in large part, on extrathyroidal conversion of thyroxine (T4) to the biological active hormone triiodothyronine (T3), catalyzed by iodothyro- nine deiodinases type 1 (D1) and type 2 (D2) [6]. These enzymes are of extreme importance to thyroid hormone action, not only as a source of plasma T3 but also, especially in the case of D2, for providing intracellular T3 in specific tissues. It has been demonstrated that leptin has stimulatory effects on the hypothalamic-pituitary-thyroid axis in animals and humans [7–12] and, most evidence indicate that leptin acts mainly by stimulating TRH synthesis and secretion [13–15]. Recently, it has been suggested that during fasting, leptin depletion together with high corticosterone levels are responsible for increased hypothalamic D2 [16], an important mechanism to maintain suppressed TRH in fasting, even in the presence of decreased Affiliation 1 Laborato ´ rio de Endocrinologia Molecular, Instituto de Biofı ´sica Carlos Chagas Filho, UFRJ, CCS, Bloco G, Cidade Universita ´ ria, Rio de Janeiro, RJ, Brazil 2 Laborato ´ rio de Fisiologia Endo ´ crina, Departamento de Cie ˆncias Fisiolo ´ gicas, Instituto de Biologia Roberto Alca ˆntara Gomes, UERJ, Rio de Janeiro, RJ, Brazil Correspondence Carmen C. Pazos de Moura Á Laborato ´ rio de Endocrinologia Molecular Á Instituto de Biofı ´sica Carlos Chagas Filho Á UFRJ, CCS, Bloco G Á Cidade Universita ´ ria Á Ilha do Funda ˜o Á CEP 21949 Á 900 Á Rio de Janeiro, RJ Á Brazil Á Tel.: +55/21/25 60 80 93 ext. 213 Á Fax: + 55/21/22 80 81 93 Á E-mail: cpazosm@biof.ufrj.br Received 24 November 2005 Á Accepted after revision 14 February 2006 Bibliography Horm Metab Res 2006; 38: 481–485 r Georg Thieme Verlag KG Stuttgart Á New York Á DOI 10.1055/s-2006-949527 Á ISSN 0018-5043 Leptin Acute Modulation of the 5 0 -deiodinase Activities in Hypothalamus, Pituitary and Brown Adipose Tissue of Fed Rats A. Cabanelas 1 P. C. Lisboa 2 E. G. Moura 2 C. C. Pazos-Moura 1 Original Basic 481 Downloaded by: University of Arizona Library. Copyrighted material.