Regulation of Cell Functions
Enrique Pimentel in Handbook of Growth Factors, 2017
The thyroid hormones are essential for the growth, development, and metabolism of vertebrates. The biosynthesis and secretion of thyroid hormones have been characterized in detail.635,636 There are two molecular species of thyroid hormones: 3,3’,5-triiodo-L-thyronine (T3) and L-thyroxine (T4). Although the main hormone secreted by the thyroid is T4, T3 is the main active thyroid hormone at the cellular level. Both T4 and T3 circulate in the blood, but the levels of T4 are two orders of magnitude higher than those of T3. The T3 present in blood is originated partially from direct thyroid secretion but peripheral intracellular deiodination processes may contribute to maintain circulating T3 levels. Thyroglobulin, the protein precursor of thyroid hormones in the thyroid gland, is a dimeric glycoprotein of 2 × 330 kDa.637 The human thyroglobulin gene is located on chromosome region 8q24, distal to the c-myc proto-oncogene locus.
Thyroid Failure and Clinical Misdiagnosis
Mark S. Gold, R. Bruce Lydiard, John S. Carman in Advances in Psychopharmacology: Predicting and Improving Treatment Response, 2018
There are two active forms of circulating thyroid hormone, l-Thyroxine (T4) and Triiodothyronine (T3). The thyroid gland secretes primarily, but not exclusively, T4, and about one third of this T4 undergoes conversion to T3 by deiodination in peripheral tissues, such as the liver and kidney. T3 is now felt to provide most of the actual thyroid hormone activity in peripheral tissues. Although T4 is secreted at eight to ten times the rate of T3, T3 is three to four times more potent.25 Both T3 and T4 are bound to serum proteins such as Thyroid Binding Globulin (TBG) and Thyroid Binding Prealbumin (TBPA). Only a relatively small fraction of the total pool of T3/T4 is actually free in the circulation and available to bind receptor sites. It is of interest to note that approximately 40% of the T4 is converted by deiodination of the inner ring into reverse T3, an apparently inactive form of the T3 hormone which is only now being studied in psychiatric and thyroid illnesses. Whether excessive conversion to reverse T3 can produce a functionally hypothyroid state in the presence of a blunted TRH test is unknown.
Regulation of the Pituitary Gland by Dopamine
Nira Ben-Jonathan in Dopamine, 2020
The hypothalamo-pituitary-thyroid axis (HPT) consists of hypothalamic TRH, pituitary TSH and the thyroid hormones, thyroxine (T4), and triiodothyronine (T3). TSH is a glycoprotein hormone made of two subunits with structural similarities to LH and FSH. TSH is produced by pituitary thyrotrophs and its main target is the TSH receptor, found primarily in the follicular cells of the thyroid gland. TSH stimulates production and secretion of the thyroid hormones, which affect almost every tissue in the body and act to increase basal metabolic rate, protein synthesis, neural maturation, and proper development and differentiation of multiple cells. Both thyrotrophs and TSH are primarily stimulated by hypothalamic TRH and inhibited by thyroid hormones.
Toward a science-based testing strategy to identify maternal thyroid hormone imbalance and neurodevelopmental effects in the progeny – part I: which parameters from human studies are most relevant for toxicological assessments?
Published in Critical Reviews in Toxicology, 2020
Ursula G. Sauer, Alex Asiimwe, Philip A. Botham, Alex Charlton, Nina Hallmark, Sylvia Jacobi, Sue Marty, Stephanie Melching-Kollmuss, Joana A. Palha, Volker Strauss, Bennard van Ravenzwaay, Gerard Swaen
The thyroid gland is an endocrine organ present in all vertebrates. Thyroxine (T4) is the main thyroid hormone synthesised and secreted by the thyroid, whereas triiodothyronine (T3), the biologically active hormone, is mostly produced by deiodination of T4 in peripheral tissues. A major role of the thyroid hormones is to regulate metabolism, e.g. during growth and reproduction. In developing offspring, rodent data (with supporting evidence in humans) indicate that thyroid hormones play a role in neuronal migration, cellular differentiation (e.g. of neurons) and glial myelination. The thyroid gland is controlled by the pituitary [through secretion of thyroid stimulating hormone (TSH)] which, in turn, is regulated by the thyrotropin releasing hormone secreted by the hypothalamus (Dickhoff and Darling 1983; DeGroot and Jameson 2001). Thyroid hormones are highly hydrophobic and therefore generally bound to serum binding proteins when circulating in the bloodstream, whereas only a minor fraction (<1%) remains as free hormones (e.g. free T4 (fT4) and free T3). It is the free hormone fraction that is sensed by the tissues, triggering the homeostatic regulatory mechanisms (Stockigt 2001).
Immunity and inflammation predictors for short-term outcome of stroke in young adults
Published in International Journal of Neuroscience, 2018
Xiaoqing Zhou, Fang Yu, Xianjing Feng, Junyan Wang, Zhibin Li, Qiong Zhan, Jian Xia
Decreased levels of FT3 were associated with an increased risk of not only severe IS but also poor outcome. In contrast, we found that neither FT4 nor TSH level were associated with stroke severity upon admission or functional outcome at 14 days after stroke onset. Acute illnesses can induce a decreased peripheral conversion of FT4 to FT3 in the absence of a primary thyroid disorder, indicating that FT3 may be more sensitive to the influence of critical illness than FT4, TSH and total thyroid hormone fractions. Possible mechanism is that thyroid hormones play a crucial role in physiological growth, development, metabolism and cellular energetics. T3 is especially required for the generation and maturation of new neurons and axonal myelination [36]. The peri-infarct zone mimics early stages of development in the brain with increased plasticity and a permissive microenvironment for remodeling [37]. Increasing evidence suggests that thyroid hormone levels are closely associated with brain acetylcholine activity, cholinergic function and the secretion of various neurotrophic factors such as nerve growth factor [38,39].
An assay for screening xenobiotics for inhibition of rat thyroid gland peroxidase activity
Published in Xenobiotica, 2020
Roger J. Price, Rachel Burch, Lynsey R. Chatham, Larry G. Higgins, Richard A. Currie, Brian G. Lake
The thyroid gland produces the hormones L-thyroxine (3,3′,5,5′-tetraiodo-L-thyronine; T4) and triiodo-L-thyronine (3,3′,5-triodo-L-thyronine; T3). Thyroid hormones are involved in important physiological processes including regulation of energy metabolism, growth and differentiation, and development and maintenance of brain function (DeVito et al., 1999; Miller et al., 2009). Chemicals may disrupt thyroid gland function by a number of modes of action including interference with thyroid hormone synthesis or secretion, increased thyroid hormone catabolism and excretion, and disruption of the conversion of T4 to T3 (Capen, 2001; DeVito et al., 1999; Miller et al., 2009). In terms of inhibition of thyroid hormone synthesis, a number of chemicals have been shown to inhibit thyroid peroxidase (TPO) activity (EC 1.11.1.8). TPO catalyses the iodination of tyrosyl residues in thyroglobulin (forming mono- and di-iodinated forms) followed by coupling of the iodotyrosyl residues to form the thyroid hormones (Capen, 2001; Taurog et al., 1996). Known inhibitors of TPO include the antihyperthyroid drugs 6-propyl-2-thiouracil (PTU) and methimazole (MMI), anti-bacterial agents, flavonoids, isoflavones, industrial chemicals and some pesticides (Capen, 2001; Divi & Doerge, 1996; Divi et al., 1997; Doerge & Decker, 1994; Freyberger & Ahr, 2006; Paul et al., 2013, 2014).
Related Knowledge Centers
- Anterior Pituitary
- Triiodothyronine
- Catecholamine
- Metabolism
- Thyroid
- Tyrosine
- Hypothalamus
- Thyroid-Stimulating Hormone
- Thyrotropin-Releasing Hormone
- Hormone