Thyroid hormone receptors multiple

Lazar MA. Thyroid hormone receptors Multiple forms, multiple possibilities. Endocrine Rev 1993 14 184-93. 

M. A. Lazar Thyroid hormone receptors multiple forms, multiple possibilities. Endocrine Review 14,184 (1993). 

The vitamin D receptor- RXR heterodimer binds in 5 RXR-VDR3 polarity to a direct repeat hormone response element However, the vitamin D receptor also forms heterodimers with the retinoic acid receptor and the thyroid hormone receptor. All three vitamin D receptor dimers can interact with either direct repeat or inverted palindromic hormone response elements. In heterodimers, the vitamin D receptor may be at the 5 -position or 3 -position, resulting in six types of activated vitamin D receptor dimers that can bind to two types of response elements, raising the possibility of multiple signaling pathways (Carlberg, 1996 Carlberg et al., 2001 Yamada et al., 2001b). 

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 class III cytokine receptor family includes two TNE receptors, the low affinity NGE receptor and 7-ceU surface recognition sites that appear to play a role in proliferation, apoptosis, and immunodeficiency. TNE-a (- 17, 000 protein) is produced by astrocytes and microglia and can induce fever, induce slow-wave sleep, reduce feeding, stimulate prostaglandin synthesis, stimulate corticotrophin-releasing factor and prolactin secretion, and reduce thyroid hormone secretion. TNE-a stimulates IL-1 release, is cytotoxic to oligodendrocytes, and reduces myelination this has been impHcated in multiple sclerosis and encephalomyelitis. Astrocyte TNE-a receptors mediate effects on IL-6 expression and augment astrocytic expression of MHC in response to other stimulants such as lEN-y. 

PR, AR, GR, MR), thyroid hormone (TRa and j8), and retinoid (RARot, jS, and 7, and RXRa) receptor superfamily of nuclear transcriptional factors (207-210), multiple members of the interleukin cytokine receptor family (211), and subtypes of the glutamate (212) and adenosine (213)receptor families. The importance of access to human cloned receptors continues to be underscored as receptor binding plays an increasingly critical role in modern drug discovery (214). 

The steroid receptor superfamily comprises the glucocorticoid (GR), progesterone (PR), mineralocorticoid (MR), androgen (AR), thyroid hormone (TR),and vitamin Dg (VDR) receptors (60). These receptors bind to steroid hormones and are translocated to the nucleus where they bind to hormone responsive elements on DNA promoter regions to alter gene expression. While steroids are very effective anti-inflammatory agents, they have a multiplicity of serious side effects that limit their full use. 

Two distinct genes encode 2 families of TRs, TRa and TRp, and both genes encode multiple receptor isoforms. Certain isoforms (e.g., TR j and TRPj) are found in virtually all thyroid hormone-responsive tissues, whereas TRp is expressed only in the anterior pituitary. Resistance to thyroid hormone has been described in patients with mutations in the TRp gene. In addition to nuclear receptor-mediated actions, there are several well-characterized, nongenomic actions of thyroid hormones, including those occurring at the plasma membrane and on the cellular cytoarchitecture. 

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