Environmental chemicals targeting thyroid

Abstract

Thyroid hormones (THs) are required for normal brain and somatic development and for the proper regulation of physiology in both children and adults. Thyroid function is controlled by the dynamic interrelationships between the hypothalamus, the pituitary and the thyroid. These dynamic relationships maintain circulating levels of THs within a narrow range under normal conditions. Normally, there is likely to be a tight relationship between changes in circulating levels of THs and changes in TH action in various target tissues. This relationship is maintained by tissue-level mechanisms that include TH metabolism and transport. Environmental chemicals that interfere with TH signaling mechanisms (Endocrine Disrupting chemicals, EDcs) may produce adverse effects both in the individual and in a population. Because of the complex nature of the regulation of thyroid function and TH action, the consequences of EDc exposure is also likely to be complex and our ability to understand these effects as well as to screen for potential EDcs must consider this complexity. Specifically, if there are chemicals in the environment that directly interfere with TH action through their receptors but do not affect circulating TH levels, they would not be identified as thyroid toxicants by currently applied screening methods or by epidemiological studies. The goal of this review is therefore to identify the issues that must be clearly resolved before effective risk assessment can be performed. HORMONES 2010, 9(1) the hypothalamic pituitaRy thyRoid axis (hpt) axis To develop efficient risk assessment strategies for thyroid toxicants, it is important to understand both the normal functioning of the hypothalamic-pituitary-thyroid axis (HPT) and what we know about individual thyroid toxicants. To this end, background information about the HPT axis and its relevance to thyroid toxicology is reviewed here. Key words: Thyroid hormones, Endocrine disruptors, Environmental chemicals, Thyroid toxicants ReviewCirculating levels of Thyroid Hormones (THs) are maintained within a relatively narrow range 1 in large part by a negative feedback relationship between circulating levels of THs and those of Thyroid Stimulating Hormone (TSH). THs appear to exert this effect by acting on one subtype of the TH receptor (TR). TRs are encoded by two separate genes,  and , the primary transcripts of which are alternatively spliced

ANIMAL MODELS OF DISEASE: Feline hyperthyroidism: an animal model for toxic nodular goiter

“…These results suggest that decreased amounts of Ga i may remove the negative inhibition of adenylyl cyclase and result in increased cAMP formation, which could contribute to the nodular growth in some hyperthyroid cats (Hammer et al 2000, Ward et al 2005b, 2010. In both of these studies, only five hyperthyroid cats were used, and unfortunately, we do not know whether any of the cats had activating mutations of either the TSHR or GNAS.…”

“…Chronic exposure to thyroid-disrupting compounds in the diet, drinking water, or environment may also play a role in the pathogenesis of feline thyroid nodules and hyperthyroidism, as postulated to occur in human thyroid disease (Diamanti-Kandarakis et al 2009, Jugan et al 2010, Zoeller 2010. For example, the polyphenolic compound bisphenol A, which is used as a plasticizer in can linings, has been detected in canned cat food and may act as a thyroid disruptor (Edinboro et al 2004, Schecter et al 2010.…”

Epidemiological trends of iodine-related thyroid disorders: an example from Slovenia

“…Endocrine disrupting chemicals most often affect the NIS, TPO, transport protein transthyretin, deiodinases, and thyroid hormone receptors (4,38).…”

Regulation of TRH neurons and energy homeostasis-related signals under stress

“…Improvements and standardized housing conditions seem required to define adequate controls and obtain reproducible data between different laboratories, together with adequate reports of the animals' age and body weight, as some correspond to the adolescent period (McCutcheon & Marinelli 2009). Another recently discovered but very important problem is the materials used in animal houses such as water bottles made of polycarbonate that release chemicals that act as endocrine disruptors causing deleterious effects, particularly during development (Zoeller 2010), and the differential leakage that occurs depending on the state and treatment of the bottle (Guart et al 2013).…”