Thyroid homeostasis

Animal studies have shown that the immune system is sensitive to exposure. Mice fed diets containing 50 or 5 00 ppm technical-grade pentachlorophenol showed greatly reduced immunocompetence in the form of increased susceptibility to the growth of transplanted tumors. Oral and intraperitoneal administration to animals causes adverse effects on thyroid homeostasis and on the thyroid gland. Competition for serum protein thyroxine binding sites may account for the antithyroid effects of pentachlorophenol. ... 

Conventional rodent toxicity studies characterize adverse effects of a chemical primarily on apical endpoints such as clinical signs or pathological states. Evidence of organ toxicity in the form of an apical endpoint does not always provide mechanistic understanding of the toxicity involved (see Chapter 13). The exposure of rodents in a cancer bioassay model can result in species-specific responses that are not relevant to humans (e.g., alpha2u-globulin-induced rat renal tumors) (see Chapter 18) (EPA 1991). Rodents may also have increased sensitivity to a particular toxicity pathway relative to humans (e.g., disruption of thyroid homeostasis and thyroid follicular tumors in rodents) (EPA 1998 I ARC 2001). There are rodent responses to chemical treatment in tissues where there is a high spontaneous incidence to develop... 

PCBs alter thyroid homeostasis, with the most consistent finding being the decrease in plasma T4 concentrations. 

Underwood BA, Loerch JD, Lewis KC (1979) Effects of dietary vitamin A deficiency, retinoic acid and protein quantity and quality on serially obtained plasma and liver levels of vitamin A in rats. JNutr 109 796-806 Centanni M, Maiani G, Vermiglio F, Canettieri G, Sanna AL, Moretti F, Trimarchi F, Andreoli M (1998) Combined impairment of nutritional parameters and thyroid homeostasis in mildly iodine-deficient children. Thyroid 8 155-159... 

Centanni M, Maiani G, Parkes AB, N Diaye AM, Ferro-Luzzi A, Lazarus JH (1995) Thyroid homeostasis and retinol circulating complex relationships in a severe iodine-deficient area of Senegal. J Endocrinol Invest 18 608-612... 

Factors controlling calcium homeostasis are calcitonin, parathyroid hormone(PTH), and a vitamin D metabolite. Calcitonin, a polypeptide of 32 amino acid residues, mol wt - SGOO, is synthesized by the thyroid gland. Release is stimulated by small increases in blood Ca " concentration. The sites of action of calcitonin are the bones and kidneys. Calcitonin increases bone calcification, thereby inhibiting resorption. In the kidney, it inhibits Ca " reabsorption and increases Ca " excretion in urine. Calcitonin operates via a cyclic adenosine monophosphate (cAMP) mechanism. 

The steroid hormone 1,25-dihydroxy vitamin D3 (calcitriol) slowly increases both intestinal calcium absorption and bone resorption, and is also stimulated through low calcium levels. In contrast, calcitonin rapidly inhibits osteoclast activity and thus decreases serum calcium levels. Calcitonin is secreted by the clear cells of the thyroid and inhibits osteoclast activity by increasing the intracellular cyclic AMP content via binding to a specific cell surface receptor, thus causing a contraction of the resorbing cell membrane. The biological relevance of calcitonin in human calcium homeostasis is not well established. 

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. 

Bizhanova A, Kopp P (2009) The sodium-iodide symporter NIS and pendrin in iodide homeostasis of the thyroid. Endocrinology 150 1084—1090... 

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. 

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. 

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 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. 

CaR expression is greatest in the parathyroid glands, calcitonin-secreting C-cells of the thyroid gland, and kidney, but the CaR is also found in the two other key organs that participate in calcium homeostasis gut and bone (Brown and MacLeod, 2001). This review will focus on the structure and function of the CaR, its role in normal physiology and in various disorders of Ca -sensing, and the development of CaR-based therapeutics. 

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