Hypothalamic-Pituitary-Thyroid HPT Axis

Aromatic adds and phenol-like chemicals Ability to form H-bond with AR, logP0/w = 4—7 

Diphenylmethanes DDTs bisphenol A derivatives benzophe-nones, Cl and methane position and at 4-position on each aromatic ring 

Flutamides Electron-withdrawing groups on the benzene ring (e.g., F, Cl, N02, CN), Ph-N-C-O structure 

Numerous animal studies and human clinical observations show that these hormones play an essential role in pre- and post-natal brain development in vertebrates. Thus, exposure to thyroid-acting agents during fetal life and early childhood, when normal levels of thyroid hormones are crucial to growth and neurological development, should be of greatest concern. 

Laboratory and epidemiological data suggest that various polychlorinated biphenyls, dioxins, flame retardants, pesticides (e.g., DDT), perfluorinated chemicals, phthalates, bisphenols, and ultraviolet filters may inhibit thyroid function through a variety of mechanisms [31-33]. 

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A large number of ubiquitous environmental pollutants are very toxic to the hypothalamic-pituitary-thyroid (HPT) axis when administered at high (greater than environmental) levels. To study low level effects on the HPT axis, laboratory animals were administered a mixture of 16 organochlorine pesticides and other chlorinated hydrocarbons and heavy metals, all at levels similar to those found environmentally, so as to simulate environmental exposure. The chemicals included DDT (6.91), HCB (5.73), TCDD (6.80), PCBs (6.29), methoxychlor (5.08), endosulfan (3.83), heptachlor (6.10), hexachlorocyclohexane (3.80), dieldrin (5.40), aldrin (6.50), mirex (7.18), several chlorinated benzenes (2.84-3.44), cadmium (-1.65), and lead (1.35). Effects were measured by monitoring thyroid activity. The study found that this mixture of environmental pollutants was toxic and can alter HPT physiology in sexually mature malesJ50 ... 

Thyroliberin, thyrotropin-releasing hormone, TRH, pGlu-His-Pro-NH2, produced in the paraventricular nucleus of the hypothalamus, stimulates biosynthesis and secretion of thyrotropin (TSH) from the anterior pituitary. It is central in regulating the hypothalamic-pituitary-thyroid (HPT) axis. Furthermore, TRH influences the release of other hormones, e.g., prolactin, growth hormone, vasopressin, insulin, and also the classic neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline). In addition, it is... 

Endocrine disruption Disturbances through the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-thyroid (HPT) axes Pb produces reductions in FSH, LH, testosterone, estradiol via HPG axis or steroidogenic protein, altered number of estrogen receptors there is a negative association, PbB versus T4 and free T4, via the HPT axis Srivastava et al. (2004), Biswas and Ghosh (2006), Dundar et al. (2006)... 

Thyroid hormone production is governed by the actions of the hypothalamic-pituitary-thyroid axis (HPT axis). Thyrotropin releasing hormone (TRH) synthesized by the hypothalamus is transported to the anterior pituitary, where TRF stimulates thyrotrophic cells to produce thyrotrophin (TSH). TSH is a glycoprotein with a short half-life of less than 20 min it is one of three pituitary glycoprotein hormones with alpha- and beta-subunits. These three pituitary glycoproteins (luteotrophin, fol-liotrophin, and TSH) share the same alpha-subunit. 

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