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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is suggested that in addition to stimulating the thyroid gland (i.e., the main regulator of metabolic-rate in adults) thyroid-stimulating hormone (T.S.H.) stimulates the second thermoregulatory organ (i.e., the brown adipose tissue). Brown fat functions as a thermogenic organ in hibernating animals, in newborn infants, and during cold acclimatisation. However, B.F. may persist in childhood and in some adults. Its hypertrophy in response to T.S.H. could account for certain unexplained features of myxoedema in which serum-T.S.H. is raised, such as swelling of the supraclavicular fat pad and the less commonly encountered symptoms of ascites or pericardial and pleural serous effusions which can persist for years in undiagnosed cases and respond rapidly to thyroxine when serum-T.S.H. returns to normal. Lack of thyroxine is not the cause of these features since they are not found in pituitary myxoedema, where thyroid hormone levels are as low but T.S.H. is absent.
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PMID:Possible stimulation of thermogenesis in brown adipose tissue by thyroid-stimulating hormone. 4 49

Young adult male and female Djungarian hamsters were exposed to ambient temperatures of 23 or 0 C for 12 h; half of the animals in each group were treated with iopanoic acid to suppress the peripheral conversion of T4 to the thermotropically active thyroid hormone T3 by the enzyme 5'-deiodinase (5'D). Brown adipose tissue (BAT) mRNA for uncoupling protein (UCP), BAT lipoprotein lipase (LPL) activity, and 5'D activity were measured at the conclusion of the study. A temperature of 0 C produced large rises in 5'D and LPL activities and a similar large increase in UCP mRNA within the 12-h exposure period. When 5'D activity was inhibited with iopanoic acid, mRNA for UCP was reduced, while LPL activity was unaffected. The results show that the optimal production of mRNA for BAT UCP depends on the availability of T3; however, T3 is not required for the cold-induced activation of LPL activity in BAT.
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PMID:Inhibition of 5'-deiodination of thyroxine suppresses the cold-induced increase in brown adipose tissue messenger ribonucleic acid for mitochondrial uncoupling protein without influencing lipoprotein lipase activity. 232 97

Brown adipose tissue (BAT) iodothyronine 5'-deiodinase (5'D) activities are very high during fetal life but decrease 10-fold a few hours before birth. Accordingly, BAT 3,5,3'-triiodothyronine (T3) concentrations are also very high. The temporal patterns of changes in BAT 5'-D and fetal plasma insulin are similar (and differ from the pattern for catecholamines) but are not superimposable. A causal role for insulin in the activation of fetal BAT 5'-D is therefore not supported by the data. Maternal thyroidectomy leads to a decrease in the total and relative weight of fetal BAT and to a 30-50% increase in BAT 5'-D activities; BAT thyroid hormone concentrations are essentially unchanged. Fetal hypothyroidism was induced by giving methimazole and resulted in a marked decrease of BAT thyroxine (T4) and T3 concentrations. This treatment increased BAT 5'-D activity only on day 21 of gestation, but no effect was observed on day 20. The fetal 5'-D response to thyroid hormones infused into the methimazole-treated dams was studied at 21 days of gestation. The increase in BAT 5'-D induced by methimazole treatment was prevented by T4 infused into control dams but not by T3. In fetuses from thyroidectomized dams, the pattern of 5'-D regulation by thyroid hormones was impaired. It is suggested that the high concentrations of thyroid hormones present in fetal BAT might participate in the general maturation and development of fetal BAT.
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PMID:Thyroid hormones and 5'-deiodinase in rat brown adipose tissue during fetal life. 268 35

The effects of two dietary treatments on norepinephrine turnover in iron deficiency were examined. These studies were designed to bridge the gap between previous studies of poor thermoregulation in iron deficiency which used a diet (HMW, Hubbel-Mendel-Wakeman formulation) relatively high in fat (46% of calories) and moderate in carbohydrate (46% of calories) and the more recent studies of thermogenesis in iron deficiency which use the AIN-76 recommended diet which is relatively low in fat (11% of calories) and high in carbohydrate (67% of calories). Iron deficient rats grew less well and had depressed thyroid hormone concentrations regardless of dietary treatment group. The HMW diet significantly increased norepinephrine turnover in heart in iron deficient animals relative to AIN diet but had no effect in controls. Brown adipose tissue norepinephrine turnover was threefold higher in HMW rats fed a low iron diet, and only 67 percent higher in control rats. This study demonstrates that certain modest macronutrient manipulations affect norepinephrine content and turnover more in iron deficient than controls. However, abnormalities in thyroid hormone concentrations persist in iron deficient animals regardless of these dietary treatments.
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PMID:Norepinephrine turnover in iron deficiency: effect of two semi-purified diets. 276 48

Brown adipose tissue (BAT) thermogenesis is important in the adaptation of body energy expenditure to cold exposure, fasting, and overfeeding and in the pathogenesis of obesity. Thyroid hormones are required for the normal functioning of BAT. The mechanism of their effect on BAT, however, has not yet been elucidated. Since most thyroid hormone effects are mediated via the binding of T3 to nuclear receptors (NT3R) the present studies were performed to investigate whether BAT contained NT3R and whether these NT3R were affected by cold exposure, fasting, overfeeding, or hypo- or hyperthyroidism. Rat BAT was found to contain NT3R with a maximum binding capacity (MBC) of 0.28 ng T3/mg DNA and a dissociation constant (Kd) of 3.2 X 10(-10) M. These parameters were unaffected by any of the experimental conditions studied. A major alteration of BAT NT3R MBC or Kd is thus not a causal factor in the changes in BAT thermogenesis induced by the above experimental conditions. In contrast, 3-wk overfeeding increased (+48%) and fasting decreased (-29%) the MBC of hepatic NT3R. Overfeeding increased serum T3 (+110%), while fasting decreased it (-37%).
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PMID:Brown fat nuclear triiodothyronine receptors in rats. 377 60

Brown adipose tissue (BAT) thermogenesis is activated by the sympathetic nervous system. BAT responses to norepinephrine are blunted in hypothyroidism and are rapidly restored by thyroid hormone. We examined in rats the effects of thyroid hormone on BAT beta 1- and beta 2-adrenergic receptors (AR) expression and capacity to generate cAMP in response to adrenergic stimulation. Both are reduced in hypothyroidism. The reduction in cAMP generation is equal to or greater than that in beta 1,2-AR; it is the same whether cAMP production is stimulated with norepinephrine, selective beta 3-AR agonists, or forskolin; and it is not affected by the inhibition of phosphodiesterase. Both beta 1,2-AR and the capacity to generate cAMP were slowly corrected by thyroid hormone. T3 normalized beta 1,2-AR between 1 and 2 days, whereas the improvement in cAMP generation lagged 1 or 2 days behind. Within 2 days of acclimation of athyreotic rats at 30 C, the number of beta 1,2-AR reached the euthyroid level, whereas exposure to 4 C decreased these receptors. We reached the following conclusions: 1) BAT beta 1,2-AR and capacity to generate cAMP are reduced in hypothyroidism; 2) the latter, however, is not explained by the reduction in beta 1,2-AR, but, rather, reflects a fault at the postreceptor level; 3) the reduction in beta 1.2-AR number is largely caused by the cold stress derived from the low metabolic rate of the hypothyroid state; and 4) the slow restoration of both receptor number and capacity to generate cAMP after T3 are not consistent with these defects being a significant factor in the previously reported blunted uncoupling protein responses to adrenergic stimulation in hypothyroidism.
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PMID:Effects of thyroid hormone on norepinephrine signaling in brown adipose tissue. I. Beta 1- and beta 2-adrenergic receptors and cyclic adenosine 3',5'-monophosphate generation. 762 60

Rats with graft-versus-host disease (GVHD), induced by injecting spleen cells of parental strain rats (Brown Norway) into non-irradiated (Brown Norway x Lewis) F1 hybrid rats, develop thyroiditis. This is characterized by mononuclear cell infiltration with destruction of the epithelium and a significant reduction in serum thyroid hormone levels. Immunohistochemically, the mononuclear cells consisted mainly of CD8-positive cells and macrophages. These findings provide evidence that the thyroid gland can now be enumerated as one of the target organs during GVHD. The CD8-positive cells may serve as important effector cells in lesion development, either by direct cytotoxicity or by supporting the cytotoxic potential of macrophages.
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PMID:Mononuclear cell thyroiditis in rats with graft-versus-host disease. 774 2

The mechanisms whereby thyroid hormone increases heat production have been analyzed with emphasis in more recent developments. Thyroid hormone increases obligatory thermogenesis as a result of the stimulation of numerous metabolic pathways involved in development, remodeling, and delivery of energy to the tissues. In addition, thyroid hormone may specifically stimulate some thermogenic mechanisms selected during evolution of homeotherms (e.g., Na/K-ATPase, Ca2+ cycling in muscle). Thyroid hormone also plays an essential role in facultative thermogenesis interacting with the sympathetic nervous system (SNS) at various levels. Peripherally, thyroid hormone potentiates the effects of the SNS at the level of the adrenergic receptor and adenylyl cyclase complex as well as distal from this point. Synergistic interactions between T3 and cAMP on the regulation of gene expression have been described. Brown adipose tissue (BAT) T4-5'-deiodinase plays a central role in controlling heat production. When this enzyme is stimulated by norepinephrine in the euthyroid and hypothyroid condition, it provides high concentrations of T3 to BAT; inhibition by T4 in hyperthyroidism may limit brown fat thermogenic responses. Also, thyrotoxicosis uniquely reduces the expression of beta 3-adrenergic receptors in brown adipose tissue, and the increased obligatory thermogenesis of this condition, via afferent neural pathways, may reduce the hypothalamic stimulation of brown fat, providing additional mechanisms to limit brown adipose tissue thermogenesis in hyperthyroidism.
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PMID:Thyroid hormone control of thermogenesis and energy balance. 880 1

Brown adipose tissue (BAT) expresses several adenylyl cyclase (AC) subtypes, and adrenergic stimulation selectively upregulates AC-III gene expression. Previous studies have described synergistic interactions between the sympathetic nervous system (SNS) and 3,5,3'-triiodothyronine (T3) on the regulation of gene expression in BAT. Because adrenergic stimulation also increases the activity of BAT type II thyroxine 5'-deiodinase (DII) and local T3 generation is important for many functional responses in BAT, we examined the effects of thyroid hormone status on the expression of various AC subtypes. Hypothyroidism selectively increased AC-III mRNA levels in BAT but not in white adipose tissue. Of the other subtypes examined, hypothyroidism did not alter AC-VI mRNA levels and slightly reduced AC-IX mRNA levels in BAT. The increase in AC-III expression was paralleled by an increase in forskolin-stimulated AC activity in BAT membranes. Sympathetic denervation of BAT abolished the increase in both AC activity and AC-III mRNA expression produced by hypothyroidism, but did not affect the expression of other subtypes. Surgical denervation also prevented the induction of AC-III in the cold-stressed euthyroid rat, but injections of T3 failed to alter AC-III expression in intact or denervated BAT. Our results indicate that T3 does not directly affect expression of AC-III. Rather, hypothyroidism increases BAT AC-III expression indirectly via an increase in sympathetic stimulation. Furthermore, our results strongly indicate that the increase in AC activity in hypothyroid BAT is due to increased expression of AC-III.
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PMID:Effect of hypothyroidism on adenylyl cyclase activity and subtype gene expression in brown adipose tissue. 927 66

In newborns and small mammals, cold-induced adaptive (or nonshivering) thermogenesis is produced primarily in brown adipose tissue (BAT). Heat production is stimulated by the sympathetic nervous system, but it has an absolute requirement for thyroid hormone. We used the thyroid hormone receptor-beta--selective (TR-beta--selective) ligand, GC-1, to determine by a pharmacological approach whether adaptive thermogenesis was TR isoform--specific. Hypothyroid mice were treated for 10 days with varying doses of T3 or GC-1. The level of uncoupling protein 1 (UCP1), the key thermogenic protein in BAT, was restored by either T3 or GC-1 treatment. However, whereas interscapular BAT in T3-treated mice showed a 3.0 degrees C elevation upon infusion of norepinephrine, indicating normal thermogenesis, the temperature did not increase (<0.5 degrees C) in GC-1--treated mice. When exposed to cold (4 degrees C), GC-1--treated mice also failed to maintain core body temperature and had reduced stimulation of BAT UCP1 mRNA, indicating impaired adrenergic responsiveness. Brown adipocytes isolated from hypothyroid mice replaced with T3, but not from those replaced with GC-1, had normal cAMP production in response to adrenergic stimulation in vitro. We conclude that two distinct thyroid-dependent pathways, stimulation of UCP1 and augmentation of adrenergic responsiveness, are mediated by different TR isoforms in the same tissue.
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PMID:Thyroid hormone--sympathetic interaction and adaptive thermogenesis are thyroid hormone receptor isoform--specific. 1143 54


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