Hypothyroidism causes CNS features because of presence of which receptor in brain?
Thyroid hormones enter cells and T3 binds to thyroid receptors (TR) in the nuclei. T4 can also bind, but not as avidly. The hormone-receptor complex then binds to DNA zinc fingers and increases (or in some cases, decreases) the expression of a variety of different genes that code for proteins that regulate cell function (see Chapter 1). Thus, the nuclear receptors for thyroid hormones are members of the superfamily of hormone-sensitive nuclear transcription factors. There are two human TR genes: an a receptor gene on chromosome 17 and a b receptor gene on chromosome 3. By alternative splicing, each forms at least two different mRNAsand therefore two different receptor proteins. TRb2 is found only in the brain, but TRa1, TRa2, and TRb1 are widely distributed. TRa2 differs from the other three in that it does not bind T3 and its function is not yet fully established. TRs bind to DNA as monomers, homodimers, and heterodimers with other nuclear receptors, paicularly the retinoid X receptor (RXR). The TR/RXR heterodimer does not bind 9-cis retinoic acid, the usual ligand for RXR, but TR binding to DNA is greatly enhanced in response to thyroid hormones when the receptor is in the form of this heterodimer. There are also coactivator and corepressor proteins that affect the actions of TRs. Presumably, this complexity underlies the ability of thyroid hormones to produce many different effects in the body. In most of its actions, T3 acts more rapidly and is three to five times more potent than T4.REF: GANONG&;S REVIEW OF MEDICAL PHYSIOLOGY, KIM BARRETT, HEDDWEN BROOKS, SCOTT BOITANO, SUSAN BARMANTWENTY THIRD EDITIONPAGE NO:308,309
TR alpha 1
TR alpha 2
TR beta 1
TR beta 2
Endocrinology