Thyroid hormone receptors brain

Carrasco, E., Blum, M., Weickert, C. S., and Casper, D. (2003). Epidermal growth factor receptor expression is related to post-mitotic events in cerebellar development Regulation by thyroid hormone. Brain Res. Dev. Brain Res. 140, 1-13. 

Thyroid hormone receptors (THRs) are subdivided intoa and P types, each having two isoforms. In rat brain, THR, mRNA is present in hippocampus, hypothalmus, cortex, cerebellum, and amygdala. Thyroxine (l-T (284) and triiodothyronine (l-T ) (285) are endogenous ligands for the THRs. TRIAC (286) is a THR antagonist. Selective ligands for PPARs have yet to be identified (Table 16). 

Cell fractionation procedures were fundamental to the biochemical identification of steroid and thyroid hormone receptors in brain as well as in other tissues. Isolation of highly purified cell nuclei from small amounts of tissue from discrete brain regions generally is accomplished with the aid of a nonionic detergent, such as Triton X-100 [7],... 

Like steroid hormones, thyroid hormones interact with receptors to alter genomic activity and affect the synthesis of specific proteins during development [25-28], As with testosterone and progesterone, metabolic transformation of thyroxine (T4) is critical to its action [25-28]. Moreover, as with steroid hormones, thyroid hormones alter brain functions in adult life in ways that both resemble and differ from their action during development [25-28]. 

The adult brain is endowed with nuclear as well as cytosolic and membrane T3 receptors that have been visualized by autoradiography and studied biochemically [30-33]. Both neurons and neuropil are labeled by [ 1251]T3, and the labeling is selective across brain regions. Functionally, one of the most prominent features of neural action of thyroid hormone in adulthood is subsensitivity to norepinephrine as a result of a hypothyroid state [27], These changes may be reflections of loss of dendritic spines in at least some neurons of the adultbrain. Clinically, thyroid hormone deficiency increases the probability of depressive illness, whereas thyroid excess increases the probability of mania (Ch. 52) in susceptible individuals [27],... 

Large numbers of thyroid hormone receptors are found in the most hormone-responsive tissues (pituitary, liver, kidney, heart, skeletal muscle, lung, and intestine), while few receptor sites occur in hormone-unresponsive tissues (spleen, testes). The brain, which lacks an anabolic response to T3, contains an intermediate number of receptors. In congruence with their biologic potencies, the affinity of the receptor site forT4 is about ten times lower than that forT3. Under some conditions,... 

PCBs, including poly-ort/jo-substituted PCBs, which have a very low affinity for the Ah receptor, inhibit the binding of T4 to transthyretin, an important transport protein for both T4 and T3 (Chauhan et al. 2000 Cheek et al. 1999 Darnerud et al. 1996a). Inhibition of binding of thyroid hormones to transthryetin could alter hormone delivery to target tissues, including the brain, and could also result in depressed levels of serum total TT4 or TT3 (Brouwer et al. 1998). 

Thyroid hormone is essential for normal development of the human brain (Calvo, 1990 Morreale de Escobar et al. 2000). Numerous factors are involved in controlling the levels of receptor-active thyroid hormone, and disruption of any of these at critical phases of human development can lead to severe and persistent cognitive and motor deficits (Haddow, 1999). 

Since the brain contains receptors and is a developmental and homeostatic target for thyroid hormones, a mechanism must exist which discriminates between neural and peripheral tissue-specific functions under thyroid hormone control. We describe here the properties of a thyroid hormone receptor predominantly expressed in the rat brain. We also present in situ hybridization histochemistry data outlining the brain subregions containing this receptor mRNA. Its characterization implies a multiple receptor system which may help to explain some of the tissue-specific physiological effects of thyroid hormones. 

The rat brain c-erb-A polypeptides generated in vitro bound [I25l] 3 5,3-triiodo-L-thyronine with a dissociation constant of 3 X 10" Mt approximating the binding affinity for the thyroid hormone receptor isolated from tissue culture cells (36, 3. Competition for th various thyroid hormone... 

Rat Thyroid Hormone Receptor mRNA is Abundant in the Brain... 

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