Female sex hormones mediate the allergic lung reaction by regulating the release of inflammatory mediators and the expression of lung E-selectin in rats

Background: Fluctuations of estradiol and progesterone levels caused by the menstrual cycle worsen asthma symptoms. Conflicting data are reported in literature regarding pro and anti-inflammatory properties of estradiol and progesterone. Methods: Female Wistar rats were ovalbumin (OVA) sensitized 1 day after resection of the ovaries (OVx). Control group consisted of sensitized-rats with intact ovaries (Sham-OVx). Allergic challenge was performed by aerosol (OVA 1%, 15 min) two weeks later. Twenty four hours after challenge, BAL, bone marrow and total blood cells were counted. Lung tissues were used as explants, for expontaneous cytokine secretion in vitro or for immunostaining of E-selectin. Results: We observed an exacerbated cell recruitment into the lungs of OVx rats, reduced blood leukocytes counting and increased the number of bone marrow cells. Estradiol-treated OVx allergic rats reduced, and those treated with progesterone increased, respectively, the number of cells in the BAL and bone marrow. Lungs of OVx allergic rats significantly increased the E-selectin expression, an effect prevented by estradiol but not by progesterone treatment. Systemically, estradiol treatment increased the number of peripheral blood leukocytes in OVx allergic rats when compared to non treated-OVx allergic rats. Cultured-BAL cells of OVx allergic rats released elevated amounts of LTB(4) and nitrites while bone marrow cells increased the release of TNF-alpha and nitrites. Estradiol treatment of OVx allergic rats was associated with a decreased release of TNF-alpha, IL-10, LTB4 and nitrites by bone marrow cells incubates. In contrast, estradiol caused an increase in IL-10 and NO release by cultured-BAL cells. Progesterone significantly increased TNF-alpha by cultured BAL cells and bone marrow cells. Conclusions: Data presented here suggest that upon hormonal oscillations the immune sensitization might trigger an allergic lung inflammation whose phenotype is under control of estradiol. Our data could contribute to the understanding of the protective role of estradiol in some cases of asthma symptoms in fertile ans post-menopausal women clinically observed.

The case of thyroid hormones: how to learn physiology by solving a detective case

Lellis-Santos C, Giannocco G, Nunes MT. The case of thyroid hormones: how to learn physiology by solving a detective case. Adv Physiol Educ 35: 219-226, 2011; doi:10.1152/advan.00135.2010.Thyroid diseases are prevalent among endocrine disorders, and careful evaluation of patients' symptoms is a very important part in their diagnosis. Developing new pedagogical strategies, such as problem-based learning (PBL), is extremely important to stimulate and encourage medical and biomedical students to learn thyroid physiology and identify the signs and symptoms of thyroid dysfunction. The present study aimed to create a new pedagogical approach to build deep knowledge about hypo-/hyperthyroidism by proposing a hands-on activity based on a detective case, using alternative materials in place of laboratory animals. After receiving a description of a criminal story involving changes in thyroid hormone economy, students collected data from clues, such as body weight, mesenteric vascularization, visceral fat, heart and thyroid size, heart rate, and thyroid-stimulating hormone serum concentration to solve the case. Nevertheless, there was one missing clue for each panel of data. Four different materials were proposed to perform the same practical lesson. Animals, pictures, small stuffed toy rats, and illustrations were all effective to promote learning, and the detective case context was considered by students as inviting and stimulating. The activity can be easily performed independently of the institution's purchasing power. The practical lesson stimulated the scientific method of data collection and organization, discussion, and review of thyroid hormone actions to solve the case. Hence, this activity provides a new strategy and alternative materials to teach without animal euthanization.

Exploiting pi-acceptors for the determination of thyroid hormones (T3 and T4) using a single interface flow system

A fully automated methodology was developed for the determination of the thyroid hormones levothyroxine (T4) and liothyronine (T3). The proposed method exploits the formation of highly coloured charge-transfer (CT) complexes between these compounds, acting as electron donors, and pi-acceptors such as chloranilic acid (CIA) and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ). For automation of the analytical procedure a simple, fast and versatile single interface flow system (SIFA)was implemented guaranteeing a simplified performance optimisation, low maintenance and a cost-effective operation. Moreover, the single reaction interface assured a convenient and straightforward approach for implementing job`s method of continuous variations used to establish the stoichiometry of the formed CT complexes. Linear calibration plots for levothyroxine and liothyronine concentrations ranging from 5.0 x 10(-5) to 2.5 x 10(-4) mol L(-1) and 1.0 x 10(-5) to 1.0 x 10(-4) mol L(-1), respectively, were obtained, with good precision (R.S.D. <4.6% and <3.9%) and with a determination frequency of 26 h(-1) for both drugs. The results obtained for pharmaceutical formulations were statistically comparable to the declared hormone amount with relative deviations lower than 2.1%. The accuracy was confirmed by carrying out recovery studies, which furnished recovery values ranging from 96.3% to 103.7% for levothyroxine and 100.1% for liothyronine. (C) 2009 Elsevier B.V. All rights reserved.

Occurrence of Sexual Hormones in Sediments of Mangrove in Brazil

The presence of sexual hormones (female estrogens) was assessed in sediments of a mangrove located in the urban region of southern Brazil. The estrogens are involved in human sexual reproduction. They act as the chemical messengers, and they are classified as natural and synthetic. The estrogens inputs in the environment are from treated and untreated sewage. The presence of estrogens in sewage is excretion from the female due to natural production and use of contraceptives (synthetic estrogens). With the indiscriminate release of sewage into the environment, estrogens can be found in rivers, lakes, and even in oceans. In this work, the presence of estrone (E1), 17-beta-estradiol (E2), and 17-alpha-ethynilestradiol (EE2) in eight sedimentary stations in Itacorubi mangrove located on Santa Catarina Island, south Brazil, was investigated. Historically, the Itacorubi mangrove has been impacted by anthropogenic activities because the mangrove is inserted in the urban area of the Florianopolis. The estrogen EE2, used as contraceptive, had the highest concentration in mangrove sediment, 129.75 +/- 3.89 ng/g. E2 was also found, with its concentration ranging from 0.90 +/- 0.03 to 39.77 +/- 1.19 ng/g. Following the mechanism, under aerobic or anaerobic conditions, E2 will first be oxidized to E1, which is further oxidized to unknown metabolites and finally to CO(2) and water (mineralized). EE2 is oxidized to unknown metabolites and also finally mineralized. Theoretically, under anaerobic conditions, EE2 can be reduced to E1 even in environments such as mangrove which is essentially anaerobic.

Influence of anabolic steroid treatment associated to physical exercise in the ultrasonic vocalization of rats

Unlike humans, who communicate in frequency bands between 250 Hz and 6 kHz, rats can communicate in frequencies above 18 kHz. Their vocalization types depend on the context and are normally associated to subjective or emotional states. It was reported significant vocal changes due to administration of replacement testosterone in a trained tenor singer with hypogonadism. Speech-Language Pathology clinical practices are being sought by singers who sporadically use anabolic steroids associated with physical exercise. They report difficulties in reaching and keeping high notes, ""breakage"" in the passage of musical notes and post singing vocal fatigue. Those abnormalities could be raised by the association of anabolic steroids and physical exercise. Thus, in order to verify if this association could promote vocal changes, maximum, minimum and fundamental frequencies and call duration in rats treated with anabolic steroids and physically trained (10 weeks duration) were evaluated. The vocalizations were obtained by handling the animals. At the end of that period, rats treated and trained showed significant decrease in call duration, but not in other parameters. The decrease in call duration could be associated to functional alterations in the vocal folds of treated and trained animals due to a synergism between anabolic steroids and physical training. (C) 2010 Acoustical Society of America. [DOI: 10.1121/1.3488350]

Anabolic steroid associated to physical training induces deleterious cardiac effects

DO CARMO, E. C., T. FERNANDES, D. KOIKE, N. D. DA SILVA JR., K. C. MATTOS, K. T. ROSA, D. BARRETTI, S. F. S. MELO, R. B. WICHI, M. C. C. IRIGOYEN, and E. M. DE OLIVEIRA. Anabolic Steroid Associated to Physical Training Induces Deleterious Cardiac Effects. Med. Sci. Sports Exerc., Vol. 43, No. 10, pp. 1836-1848, 2011. Purpose: Cardiac aldosterone might be involved in the deleterious effects of nandrolone decanoate (ND) on the heart. Therefore, we investigated the involvement of cardiac aldosterone, by the pharmacological block of AT1 or mineralocorticoid receptors, on cardiac hypertrophy and fibrosis. Methods: Male Wistar rats were randomized into eight groups (n = 14 per group): Control (C), nandrolone decanoate (ND), trained (T), trained ND (TND), ND + losartan (ND + L), trained ND + losartan (TND + L), ND + spironolactone (ND + S), and trained ND + spironolactone (TND + S). ND (10 mg.kg(-1).wk(-1)) was administered during 10 wk of swimming training (five times per week). Losartan (20 mg.kg(-1).d(-1)) and spironolactone (10 mg.kg(-1).d(-1)) were administered in drinking water. Results: Cardiac hypertrophy was increased 10% by using ND and 17% by ND plus training (P < 0.05). In both groups, there was an increase in the collagen volumetric fraction (CVF) and cardiac collagen type III expression (P < 0.05). The ND treatment increased left ventricle-angiotensin-converting enzyme I activity, AT1 receptor expression, aldosterone synthase (CYP11B2), and 11-beta hydroxysteroid dehydrogenase 2 (11 beta-HSD2) gene expression and inflammatory markers, TGF beta and osteopontin. Both losartan and spironolactone inhibited the increase of CVF and collagen type III. In addition, both treatments inhibited the increase in left ventricle-angiotensin-converting enzyme I activity, CYP11B2, 11 beta-HSD2, TGF beta, and osteopontin induced by the ND treatment. Conclusions: We believe this is the first study to show the effects of ND on cardiac aldosterone. Our results suggest that these effects may be associated to TGF beta and osteopontin. Thus, we conclude that the cardiac aldosterone has an important role on the deleterious effects on the heart induced by ND.

Abnormal Neurovascular Control in Anabolic Androgenic Steroids Users

NUNES ALVES, M. J. N., M. R. DOS SANTOS, R. G. DIAS, C. A. AKIHO, M. C. LATERZA, M. U. P. B. RONDON, R. L. DE MORAES MOREAU, and C. E. NEGRAO. Abnormal Neurovascular Control in Anabolic Androgenic Steroids Users. Med. Sci. Sports Exerc., Vol. 42, No. 5, pp. 865-871, 2010. Purpose: Previous studies showed that anabolic androgenic steroids (AAS) increase vascular resistance and blood pressure (BP) in humans. In this study, we tested the hypotheses 1) that AAS users would have increased muscle sympathetic nerve activity (MSNA) and reduced forearm blood flow (FBF) compared with AAS nonusers and 2) that there would be an association between MSNA and 24-h BP. Methods: Twelve AAS users aged 31 +/- 2 yr (means +/- SE) and nine age-matched AAS nonusers aged 29 T 2 yr participated in the study. All individuals were involved in strength training for at least 2 yr. AAS was determined by urine test (chromatography-mass spectrometry). MSNA was directly measured by microneurography technique. FBF was measured by venous occlusion plethysmography. BP monitoring consisted of measures of BP for 24 h. Results: MSNA was significantly higher in AAS users than that in AAS nonusers (29 +/- 3 vs 20 +/- 1 bursts per minute, P = 0.01). FBF (1.92 +/- 0.17 vs 2.77 +/- 0.24 mL.min(-1).100 mL(-1), P = 0.01) and forearm vascular conductance (2.01 +/- 0.17 vs 2.86 +/- 0.31 U, P = 0.02) were significantly lower in AAS users than that in AAS nonusers. Systolic (131 +/- 4 vs 120 +/- 3 mm Hg, P = 0.001), diastolic (74 +/- 4 vs 68 +/- 3 mm Hg, P = 0.02), and mean BP (93 +/- 4 vs 86 +/- 3 mm Hg, P = 0.005) and heart rate (74 +/- 3 vs 68 +/- 3 bpm, P = 0.02) were significantly higher in AAS users when compared with AAS nonusers. Further analysis showed that there was a significant correlation between MSNA and 24-h mean BP (r = 0.75, P = 0.002). Conclusions: AAS increases MSNA and reduces muscle blood flow in young individuals. In addition, the increase in BP levels in AAS users is associated with augmented sympathetic outflow. These findings suggest that AAS increases the susceptibility for cardiovascular disease in humans.

Alterations triggered by steroid gonadal hormones in triglycerides and the cellular immune response of Calomys callosus infected with the Y strain of Trypanosoma cruzi

Calomys callosus is a wild rodent found naturally infected with different Trypanosoma cruzi strains. In the work described here, groups of male and female C callosus were subjected to orchiectomy, ovariectomy and sham operation. One month after surgery, animals were inoculated intraperitoneally (i.p.) with 4 x 10(4) blood trypomastigotes of the ""Y"" strain of T. cruzi. Parasitemia, triglycerides, nitric oxide (NO) and concanavalin A (ConA)-induced proliferation were evaluated. Parasitemia during the course of infection was significantly higher in infected and sham operated animals as compared to infected orchiectomized animals. The opposite was observed in the ovariectomized and infected group. Orchiectomized and infected animals displayed elevated triglyceride levels, as well as a more vigorous immune response, with higher splenocyte proliferation and elevated concentrations of NO. Ovariectomy resulted in an impaired immune response, as observed by a reduction of splenocyte proliferation and NO concentration. The results suggest a pivotal role for gonadal hormones in the modulation of triglyceride levels and the magnitude of the immune response during the acute phase of T. cruzi infection. (C) 2008 Published by Elsevier B.V.

Exercise training associated with estrogen therapy induced cardiovascular benefits after ovarian hormones deprivation

Menopause is recognized as a period of increased risk for coronary heart disease. Although the benefits of exercise training in lowering cardiovascular risk factors are well established, the risks and benefits of hormone therapy have been questioned. The purpose of the present study was to investigate the effects of estrogen therapy (HT) associated or not with exercise training (ET) in autonomic cardiovascular control in ovariectomized (OVX) rats. Female rats were divided into: control, OVX, OVX+HT, OVX+ET and OVX+HT+ET. HT was performed using a 0.25 mg 8-weeks sustained release pellet. Trained groups were submitted to an 8-week exercise training protocol on treadmill. Baroreflex sensitivity (BRS) was evaluated by heart rate responses to arterial pressure (AP) changes, and vagal and sympathetic tonus by pharmacological blockade. Ovariectomy induced an AP increase (123 +/- 2 mmHg vs. 108 +/- 2 mmHg), BRS impairment (similar to 69%), sympathetic activation (similar to 100%) and vagal tonus reduction (similar to 77%) compared to controls. HT or ET normalized the changes in parasympathetic tonus. However, only the association HT + ET was able to promote normalization of AP, BRS and sympathetic tonus, as compared to controls. These results indicate that ET induces cardiovascular and autonomic benefits in OVX rats under HT, suggesting a positive role of this association in the management of cardiovascular risk factor in postmenopausal women. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Reactive oxygen and nitrogen species balance in the determination of thyroid hormones-induced cardiac hypertrophy mediated by renin-angiotensin system

Role of reactive oxygen species (ROS)/nitric oxide (NO) balance and renin-angiotensin system in mediating cardiac hypertrophy in hyperthyroidism was evaluated in an in vivo and in vitro experimental model. Male Wistar rats were divided into four groups: control, thyroid hormone, vitamin E (or Trolox, its hydrosoluble analogue), thyroid hormone + vitamin E. Angiotensin II receptor (AT1/AT2) gene expression, immunocontent of AT1/AT2 receptors, angiotensinogen, NADPH oxidase (Nox2), and nitric oxide synthase isoforms, as well as ROS concentration (hydrogen peroxide and superoxide anion) were quantified in myocardium. Thyroid hormone increased ROS and NO metabolites, iNOS, nNOS and eNOS isoforms and it was accompanied by cardiac hypertrophy. AT1/AT2 expression and the immunocontent of angiotensinogen and Nox2 were enhanced by thyroid hormone. Antioxidants reduced ROS levels, Nox2, AT1/AT2, NOS isoforms and cardiac hypertrophy. In conclusion, ROS/NO balance may play a role in the control of thyroid hormone-induced cardiac hypertrophy mediated by renin-angiotensin system. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Thyroid hormones alter the adenine nucleotide hydrolysis in adult rat blood serum

The effects of ATP, ADP, and adenosine in the processes of platelet aggregation, vasodilatation, and coronary flow have been known for many years. The sequential hydrolysis of ATP to adenosine by soluble nucleotidases constitutes the main system for rapid inactivation of circulating adenine nucleotides. Thyroid disorders affect a number of biological factors including adenosine levels in different fractions. Then, we intend to investigate if the soluble nucleotidases responsible for the ATP, ADP, and AMP hydrolysis are affected by variations in the thyroid hormone levels in blood serum from adult rats. Hyperthyroidism was induced by daily intraperitoneal injections of L-thyroxine (T4) (2.5 and 10.0 mu g/100 g body weight, respectively) for 7 or 14 days. Hypothyroidism was induced by thyroidectomy and methimazole (0.05%) added to their drinking water during 7 or 14 days. The treatments efficacy was confirmed by determination of hemodynamic parameters and cardiac hypertrophy evaluation. T4 treatment predominantly inhibited, and hypothyroidism (14 days after thyroidectomy) predominantly increased the ATP, ADP, and AMP hydrolysis in rat blood serum. These results suggest that both excess and deficiency of thyroid hormones can modulate the ATP diphosphohydrolase and 5`-nucleotidase activities in rat blood serum and consequently modulate the effects mediated by these enzymes and their products in vascular system. (C) 2010 International Union of Biochemistry and Molecular Biology, Inc.

Anabolic-androgenic steroid treatment induces behavioral disinhibition and downregulation of serotonin receptor messenger RNA in the prefrontal cortex and amygdala of male mice

Nandrolone is an anabolic-androgenic steroid (AAS) that is highly abused by individuals seeking enhanced physical strength or body appearance. Supraphysiological doses of this synthetic testosterone derivative have been associated with many physical and psychiatric adverse effects, particularly episodes of impulsiveness and overt aggressive behavior. As the neural mechanisms underlying AAS-induced behavioral disinhibition are unknown, we investigated the status of serotonergic system-related transcripts in several brain areas of mice receiving prolonged nandrolone administration. Male C57BL/6J mice received 15 mg/kg of nandrolone decanoate subcutaneously once daily for 28 days, and different sets of animals were used to investigate motor-related and emotion-related behaviors or 5-HT-related messenger RNA (mRNA) levels by real-time quantitative polymerase chain reaction. AAS-injected mice had increased body weight, were more active and displayed anxious-like behaviors in novel environments. They exhibited reduced immobility in the forced swim test, a higher probability of being aggressive and more readily attacked opponents. AAS treatment substantially reduced mRNA levels of most investigated postsynaptic 5-HT receptors in the amygdala and prefrontal cortex. Interestingly, the 5-HT(1B) mRNA level was further reduced in the hippocampus and hypothalamus. There was no alteration of 5-HT system transcript levels in the midbrain. In conclusion, high doses of AAS nandrolone in male mice recapitulate the behavioral disinhibition observed in abusers. Furthermore, these high doses downregulate 5-HT receptor mRNA levels in the amygdala and prefrontal cortex. Our combined findings suggest these areas as critical sites for AAS-induced effects and a possible role for the 5-HT(1B) receptor in the observed behavioral disinhibition.

Differential effects of female sex hormones on cellular recruitment and tracheal reactivity after formaldehyde exposure

Female sex hormones (FSHs) exert profound regulatory effects on the course of lung inflammation due to allergic and non-allergic immune responses. As pollution is one of the pivotal factors to induce lung dysfunction, in this study we investigated the modulatory role of FSHs on lung inflammation after a formaldehyde (FA) exposure. For this purpose, lung and systemic inflammatory responses were evaluated in terms of leukocytes countings in bronchoalveolar lavage (BAL), peripheral blood and bone marrow lavage from 7-day ovariectomized (OVx) and Sham-OVx rats subjected to FA inhalation for 3 consecutive days. The hypothesized link between effects of FSHs on expression of adhesion molecules and mast cells degranulation was also studied. Once exposed to FA, Sham-OVx rats increased the number of total cells recovered in BAL and of leukocytes in peripheral blood, and decreased the counts in bone marrow. By contrast, in OVx rats upon FA exposure there was a reduction of the total cells counts in BAL and of blood leukocytes: lung expressions of ICAM-1 and Mac-1 were depressed, but the number of bone marrow cells did not vary. Estradiol treatment of OVx rats increased the total cells in BAL and decreased the number of blood leukocytes, whereas the number of bone marrow cell remained unaltered. Progesterone treatment, in turn increased the total cells in BAL and blood leukocytes, but decreased the number of bone marrow cells. OVx rats exposed to FA developed tracheal hyperresponsiveness to methacholine (MCh). A similarly altered response was found between the tracheal segments of Sham-OVx rats after FA exposure and that found in tracheae of naive rats. Estradiol treatment prevented FA-induced tracheal hyperresponsiveness to MCh whereas progesterone was ineffective in this regard. In addition, OVx rats upon FA exposure significantly increased both, the ability of mast cell degranulation and serum corticosterone levels. In conclusion, it was found that FSHs act by distinct control mechanisms on FA-induced lung inflammation and tracheal hyperresponsiveness, since at low circulating levels of FSHs (such as those after OVx) there is some resistance to the development of a lung inflammatory response, but the cholinergic tracheal responsiveness is exacerbated. Our data also help to understand the involvement of FSHs on mast cells activity after pollutants exposure and add information regarding the role of FSHs on the mechanisms related to endothelium-leukocyte interactions. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Concentrações plasmáticas de testosterona, triiodotironina (T3) e tiroxina (T4) em bodes submetidos ao estresse calórico

Para verificar o efeito do estresse calórico (EC) nas concentrações plasmáticas de testosterona, triiodotironina (T3) e tiroxina (T4), oito bodes, das raças Saanen (n=4) e Alpina (n=4), foram mantidos em câmara bioclimática, sob condições de termoneutralidade (13,0ºC a 26,7ºC) durante 30 dias e, após um período (60 dias) de descanso, submetidos ao EC (23,7ºC a 34,0ºC) por 30 dias. Para minimizar as variações sazonais nos perfis hormonais devido ao fotoperíodo, durante toda fase experimental, incluindo a de adaptação em condições de termoneutralidade (30 dias), o fotoperíodo foi controlado utilizando-se alternância de dias longos (16h de luz e 8h de escuro) e de dias curtos (8h de luz e 16h de escuro) a cada 30 dias. As amostras de sangue foram coletadas duas vezes por semana durante cinco semanas. No conjunto das raças, o EC não influenciou (P>0,05) as concentrações de testosterona (1,8±0,2 vs 1,3±0,2ng/ml) e nem a de T4 (52,7±2,8 vs 50,0±2,8ng/ml). Houve declínio (P<0,01) das concentrações de T3 nos animais submetidos ao experimento (1,3±0,1 vs 1,0±0,1ng/ml), mas a redução foi observada somente nos bodes Saanen. Em ambas as raças, as concentrações de T3 e T4 variaram (P<0,01) conforme o dia da coleta das amostras de sangue. O EC foi suficiente para produzir uma resposta fisiológica com redução das concentrações plasmáticas de T3 em bodes das raças Saanen, mas não da raça Alpina, assim como não foi capaz de alterar os níveis plasmáticos de testosterona e nem de T4.

Effect of triiodothyronine on the maxilla and masseter muscles of the rat stomatognathic system

The maxilla and masseter muscles are components of the stomatognathic system involved in chewing, which is frequently affected by physical forces such as gravity, and by dental, orthodontic and orthopedic procedures. Thyroid hormones (TH) are known to regulate the expression of genes that control bone mass and the oxidative properties of muscles; however, little is known about the effects of TH on the stomatognathic system. This study investigated this issue by evaluating: i) osteoprotegerin (OPG) and osteopontine (OPN) mRNA expression in the maxilla and ii) myoglobin (Mb) mRNA and protein expression, as well as fiber composition of the masseter. Male Wistar rats (~250 g) were divided into thyroidectomized (Tx) and sham-operated (SO) groups (N = 24/group) treated with T3 or saline (0.9%) for 15 days. Thyroidectomy increased OPG (~40%) and OPN (~75%) mRNA expression, while T3 treatment reduced OPG (~40%) and OPN (~75%) in Tx, and both (~50%) in SO rats. Masseter Mb mRNA expression and fiber type composition remained unchanged, despite the induction of hypo- and hyperthyroidism. However, Mb content was decreased in Tx rats even after T3 treatment. Since OPG and OPN are key proteins involved in the osteoclastogenesis inhibition and bone mineralization, respectively, and that Mb functions as a muscle store of O2 allowing muscles to be more resistant to fatigue, the present data indicate that TH also interfere with maxilla remodeling and the oxidative properties of the masseter, influencing the function of the stomatognathic system, which may require attention during dental, orthodontic and orthopedic procedures in patients with thyroid diseases.