Thyroid hormone homeostasis

Yuan et al. [47] inferred that other e-waste-derived toxic chemicals than PBDEs may have also interfered with the balance of thyroid hormone homeostasis. However, these hypotheses still need further confirmation. 

Baneijee KK, Muthu PM. 1994. Effect of cigarette smoking on thyroid hormone homeostasis. Indian J Med Res 99 74-76. 

The lARC has determined that there is sufficient evidence for the carcinogenicity of amitrole to experimental animals and inadequate evidence for carcinogenicity to humans. It was noted that amitrole produces thyroid tumors in rodents by a nongenotoxic mechanism that involves interference with the functioning of the thyroid peroxidase, resulting in a reduction in circulating thyroid hormone concentration and an increase secretion of thyroid-stimulating hormone. Amitrole would not be expected to produce thyroid cancer in humans exposed to concentrations that do not alter thyroid hormone homeostasis. 

Polybrominated Diphenyl Ethers. Results of in vitro estrogen receptor and thyroid hormone transport protein binding assays and in vivo studies of thyroid hormone homeostasis indicate that PBDEs have the potential to disrupt normal endocrine function. 

The thyroid-pituitary-hypothalamus axis controls thyroid hormone homeostasis. Thyrotropin-releasing hormone (TRH), released from the hypothalamus, stimulates the synthesis and release of thyroid-stimulating hormone (thyrotropin, TSH) from the anterior pituitary. TSH increases the release of thyroid hormones by several mechanisms, including stimulation of the I pump. While lower than normal levels of T3 and T4 cause an exaggerated response of the pituitary to TRH, released thyroid hormones, in feedback control, blunt the stimulating action of TRH on the pituitary. For further discussion of TSH and TRH biochemistry, see, for example, the review by Kannan48. 

Neurotoxicity can also occur as a result of indirect effects. For example, damage to hepatic, renal, circulatory, or pancreatic structures may result in secondary effects on the function and structure of the nervous system, such as encephalopathy or polyneuropathy. Secondary effects would not cause a substance to be considered neurotoxic, though at high enough doses, neurotoxicity could be evident. Thus, for the purpose of this review, a substance is defined as neurotoxic when it or its metabolites produce adverse effects as a result of direct interactions with the nervous system. It should be noted, nevertheless, that some chemicals may have multiple modes of action and affect the nervous system directly and indirectly. For example, several halogenated compounds (e.g., polychlorinated biphenyls (PCB), polybrominated diphenyl ethers (PBDE)) may interact directly with brain cells, and also affect the development of the nervous system by altering thyroid hormone homeostasis.7 8... 

Wong H, Lehman-McKeeman LD, Grubb MF, et al. Increased hepatobiliary clearance of unconjugated thyroxine determines DMP 904-induced alterations in thyroid hormone homeostasis in rats. Toxicol Sci. 2005 84(2) 232-242. 

Eales, J.G., S.B. Brown, D.G. Cyr, B.A. Adams and K.R. Finnson. Deiodination as an index of chemical disruption of thyroid hormone homeostasis and thyroidal status in fish. In Environmental Toxicology and Risk Assessment Standardization of Biomarkers for Endocrine Disruption and Environmental Assessment Eighth Volume, ASTM STP 1364, edited by D.S. Henshel, M.C. Black and M.C. Harrass, West Conshohocken, PA, American Society for Testing and Materials, pp. 136-164, 1999. 

Kohn, M.C.. Effects of TCDD on thyroid hormone homeostasis in the rat. Drug Chem. Toxicol. 1 259-277, 2000. 

For chlorate, the Committee concluded that the most sensitive effects were changes to the thyroid gland of male rats. Rats are considered to be highly sensitive to the effects of agents that disrupt thyroid hormone homeostasis. The Committee considered that humans are likely to be less sensitive than rats to these effects and that a safety factor for interspecies variation was not required. However, the Committee noted deficiencies in the database, particularly with respect to investigation of possible neurodevelopmental effects. The Committee therefore established an ADI of 0-0.01 mg/kg bw for chlorate on the basis of the BMDUo of 1.1 mg/kg bw per day for non-neoplastic effects on the thyroid of male rats in a recent carcinogenicity study, a safety factor of 10 to allow for intraspecies variability and an additional factor of 10 to allow for the deficiencies in the database. 

DenBesten C, Bennik MHJ, Bruggeman I, et al. (1993) The role of oxidative metabolism in hexchlorobenzene induced porphyria and thyroid hormone homeostasis a comparison with pentachlorobenzene in a 13-week feeding study. Appl Pharmacol 119 181-194... 

Secondary to the societal concerns around chemical-related endocrine disruption, the OECD407 subacute 28-day toxicity study protocol has been updated in 2007 with parameters relating to endocrine homeostasis. Specifically, circulating thyroid hormones and detailed assessment of reproductive organ parameters were added to the protocol. Reproductive hormones were suggested as additional parameters but they were deemed not informative in view of their large variability in untreated animals. 

The major location of calcium in the body is in the skeleton, which contains more than 90% of the body calcium as phosphate and carbonate. Bone resorption and formation keeps this calcium in dynamic equilibrium with ionized and complexed calcium in blood, cellular fluids and membranes. Homeostasis is mainly regulated by the parathyroid hormone and vitamin D which lead to increased blood calcium levels, and by a thyroid hormone, calcitonin, which controls the plasma calcium concentration J5 Increasing the concentration of calcitonin decreases the blood calcium level, hence injections of calcitonin are used to treat severe hyperalcaemia arising from hyperparathyroidism, vitamin D intoxication or the injection of too high a level of parathyroid extract. High levels of calcitonin also decrease resorption of calcium from bone. Hypocalcaemia stimulates parathyroid activity, leading to increased release of calcium from bone, reduction in urinary excretion of calcium and increased absorption of calcium from the intestine. Urinary excretion of phosphate is enhanced. 

The thyroid and parathyroid glands serve a number of vital endocrine functions. The thyroid gland synthesizes and secretes the thyroid hormones T3 and T4. These hormones are important regulators of cellular metabolism and metabolic rate. Thyroid hormones also interact with other hormones to facilitate normal growth and development. The parathyroid glands control calcium homeostasis through the release of PTH. This hormone is crucial... 

The normal thyroid gland secretes sufficient amounts of the thyroid hormones—triiodothyronine (T3) and tetraiodothyronine (T4, thyroxine)—to normalize growth and development, body temperature, and energy levels. These hormones contain 59% and 65% (respectively) of iodine as an essential part of the molecule. Calcitonin, the second type of thyroid hormone, is important in the regulation of calcium metabolism and is discussed in Chapter 42 Agents That Affect Bone Mineral Homeostasis. 

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