Bio: Nilkanta Chakrabarti is an academic researcher from Bose Institute. The author has contributed to research in topics: Stimulation & Nitric oxide synthase. The author has an hindex of 1, co-authored 1 publications receiving 27 citations.
TL;DR: The present data indicate a definite role of T3 in nongenomic signal generation and transfer in mature rat cerebral cortex.
TL;DR: Genetically engineered knockin mouse models provide valuable tools to ascertain further the molecular actions of unliganded TRs in vivo that could underlie the pathogenesis of hypothyroidism.
Abstract: Cellular actions of thyroid hormone may be initiated within the cell nucleus, at the plasma membrane, in cytoplasm, and at the mitochondrion. Thyroid hormone nuclear receptors (TRs) mediate the biological activities of T3 via transcriptional regulation. Two TR genes, α and β, encode four T3-binding receptor isoforms (α1, β1, β2, and β3). The transcriptional activity of TRs is regulated at multiple levels. Besides being regulated by T3, transcriptional activity is regulated by the type of thyroid hormone response elements located on the promoters of T3 target genes, by the developmental- and tissue-dependent expression of TR isoforms, and by a host of nuclear coregulatory proteins. These nuclear coregulatory proteins modulate the transcription activity of TRs in a T3-dependent manner. In the absence of T3, corepressors act to repress the basal transcriptional activity, whereas in the presence of T3, coactivators function to activate transcription. The critical role of TRs is evident in that mutations of th...
TL;DR: This review focuses on the effects of thyroid hormones in vascular and renal systems and describes recent advances in the understanding of thyroid hormone action on nitric oxide and oxidative stress in the regulation of cardiovascular and renal function and in the long-term control of blood pressure.
Abstract: This review focuses on the effects of thyroid hormones in vascular and renal systems. Special emphasis is given to the mechanisms by which thyroid hormones affect the regulation of body fluids, vascular resistance and, ultimately, blood pressure. Vascular function is markedly affected by thyroid hormones that produce changes in vascular reactivity and endothelial function in hyper- and hypothyroidism. The hypothyroid state is accompanied by a marked decrease in sensitivity to vasoconstrictors, especially to sympathetic agonists, alteration that may play a role in the reduced blood pressure of hypothyroid rats, as well as in the preventive effects of hypothyroidism on experimental hypertension. Moreover, in hypothyroid rats, the endothelium-dependent and nitric oxide donors vasodilation is reduced. Conversely, the vessels from hyperthyroid rats showed an increased endothelium-dependent responsiveness that may be secondary to the shear-stress induced by the hyperdynamic circulation, and that may contribute to the reduced vascular resistance characteristic of this disease. Thyroid hormones also have important effects in the kidney, affecting renal growth, renal haemodynamics, and salt and water metabolism. In hyperthyroidism, there is a resetting of the pressure-natriuresis relationship related to hyperactivity of the renin-angiotensin system, which contributes to the arterial hypertension associated with this endocrine disease. Moreover, thyroid hormones affect the development and/or maintenance of various forms of arterial hypertension. This review also describes recent advances in our understanding of thyroid hormone action on nitric oxide and oxidative stress in the regulation of cardiovascular and renal function and in the long-term control of blood pressure.
TL;DR: Data indicated that NOS activity was upregulated in tissues primarily related to blood pressure control inhyperthyroid rats, suggesting that an increased NO production may contribute to the hyperdynamic circulation in hyperthyroidism and may have a protective homeostatic effect in the target organs of the hypertension that accompanies this endocrine disease.
Abstract: Objective: Thyroid disorders are accompanied by important changes in haemodynamic and cardiac functions and renal sodium handling. Since nitric oxide (NO) plays a crucial role in regulating vascular tone and renal sodium excretion, the present paper was designed to determine whether changes in the activity of NO synthase (NOS) participate in the cardiovascular and renal manifestations of thyroid disorders. Methods: We measured NOS activity in the heart (left and right ventricles), vessels (aorta and cava) and kidney (cortex and medulla) of euthyroid, hyperthyroid and hypothyroid rats after 6 weeks of treatment. NOS activity was determined by measuring the conversion of L-[ 3 H]-arginine to L-[ 3 H]citruline. Results: NOS activity was higher in all tissues from hyperthyroid rats when compared with controls, except in the right ventricle. In the hypothyroid group, NOS activity showed a more heterogeneous pattern, with significant increases in both ventricles but significant reduction in the aorta, while in the vena cava, renal cortex and medulla the enzyme activity also tended to be higher, but significance was not reached. Conclusions: These data indicated that NOS activity was upregulated in tissues primarily related to blood pressure control in hyperthyroid rats, suggesting that an increased NO production may contribute to the hyperdynamic circulation in hyperthyroidism and may have a protective homeostatic effect in the target organs of the hypertension that accompanies this endocrine disease. The aortic and renal findings in hypothyroid rats suggested a possible role for NOS in the increased peripheral resistance and the normal pressure ‐ diuresis ‐ natriuresis response of these hypotensive animals, although hypothyroidism produced a heterogeneous tissue response in NOS activity.
TL;DR: The role of THs in learning and memory is discussed and how THs may be effective in treating AD is elaborate by putting forward potential mechanisms.
Abstract: Thyroid hormones (THs) have a wide and important range of effects within the central nervous system beginning from fetal life and continuing throughout the adult life. Thyroid disorders are one of the major causes of cognitive impairment including Alzheimer's disease (AD). Several studies in recent years have indicated an association between hypothyroidism or hyperthyroidism and AD. Despite available evidence for this association, it remains unclear whether thyroid dysfunction results from or contributes to the progression of AD. This review discusses the role of THs in learning and memory and summarizes the studies that have linked thyroid function and AD. Eventually, we elaborate how THs may be effective in treating AD by putting forward potential mechanisms.
TL;DR: Beyond genomic and nongenomic effects of thyroid hormones, it is crucial for there to be an equilibrium between T3 or T4 and T1AM levels for maintaining cardiac homeostasis.
Abstract: Thyroid hormones play a wide range of important physiological activities in almost all organism. As changes in these hormones levels-observed in hypothyroidism and hyperthyroidism-promote serious derangements of the cardiovascular system, it is important to know their mechanisms of action. Although the classic genomic actions which are dependent on interaction with nuclear receptors to modulate cardiac myocytes genes expression, there is growing evidence about T(3) and T(4)-triggered nongenomic pathways, resulted from their binding to plasma membrane, cytoplasm, or mitocondrial receptors that leads to a rapidly regulation of cardiac functions. Interestingly both actions converge to amplify thyroid hormone effects on cardiovascular system. T(3) and T(4) nongenomic actions modify inotropic and chronotropic effects, cardiac action potential duration, cardiac growth, and myocyte shape by protein translation through protein kinases-dependent signaling cascades, which include PKA, PKC, PI3K, and MAPK, and changes on ion channels and pumps activity. In respect to the decreased systemic vascular resistance seen in hyperthyroidism, T(3) appears to activate NOS or ATP-sensitive K(+) channels. In addition, a novel biologically active T(4)-derived metabolite has been described, 3-iodothyronamine, T(1)AM, which also acts through membrane receptors to mediate nongenomic cardiac effects. This metabolite influences the physiological manifestations of thyroid hormone actions by inducing opposite effects from those stimulated by T(3) and T(4), such as negative inotropic and chronotropic effects. Therefore, beyond genomic and nongenomic effects of thyroid hormones, it is crucial for there to be an equilibrium between T(3) or T(4) and T(1)AM levels for maintaining cardiac homeostasis.