Isolation and Characterization of Mouse Complementary DNAs Encoding α and β Thyroid Hormone Receptors from Thyrotrope Cells: The Mouse Pituitary-Specific β2 …
WM Wood, KW Ocran, DF Gordon… - Molecular …, 1991 - academic.oup.com
WM Wood, KW Ocran, DF Gordon, EC Ridgway
Molecular endocrinology, 1991•academic.oup.comThyroid hormones (T3) and their receptors (TR) play a critical role in the function of the
pituitary gland, particularly in thyrotropes, where they regulate expression of the α-and β-
subunits of TSH. Since the pituitary gland is composed of seveal cell types, we undertook a
characterization of TR subtypes in a murine thyrotropic tumor (TtT-97), an excellent model in
which to study thyroid hormone action in thyrotropes. We screened a thyrotrope cDNA library
with rat TRα1 and TRβ1 cDNA probes and isolated cDNAs encoding the mouse TRα1 and …
pituitary gland, particularly in thyrotropes, where they regulate expression of the α-and β-
subunits of TSH. Since the pituitary gland is composed of seveal cell types, we undertook a
characterization of TR subtypes in a murine thyrotropic tumor (TtT-97), an excellent model in
which to study thyroid hormone action in thyrotropes. We screened a thyrotrope cDNA library
with rat TRα1 and TRβ1 cDNA probes and isolated cDNAs encoding the mouse TRα1 and …
Abstract
Thyroid hormones (T3) and their receptors (TR) play a critical role in the function of the pituitary gland, particularly in thyrotropes, where they regulate expression of the α- and β-subunits of TSH. Since the pituitary gland is composed of seveal cell types, we undertook a characterization of TR subtypes in a murine thyrotropic tumor (TtT-97), an excellent model in which to study thyroid hormone action in thyrotropes. We screened a thyrotrope cDNA library with rat TRα1 and TRβ1 cDNA probes and isolated cDNAs encoding the mouse TRα1 and TRβ1 isoforms as well as a partial clone corresponding to the non-T3 binding carboxy-terminal α2 variant. The polymerase chain reaction was used to amplify additional cDNAs for the specific 5′ domains of the mouse TRβ1 and the pituitary-specific TRβ2 aminoterminal variant. Using hybridization probes that discriminate between the α and β isoforms and their variants, we demonstrated that thyrotropes contain TRα1 and β2 mRNAs as well as transcripts encoding Rev-erbA, which arise by transcription from the opposite strand of the TRβ gene. In thyrotropes, the ratio of α2 to TRα1 mRNA levels more closely resembled the distribution in mouse brain than that in heart, where the mRNA levels of TRα1 and α2 are comparable. TRβ1 and TRβ2 mRNAs were detected in thyrotropes and were of similar size (∼6.4 kilobases). Despite the almost complete conservation between the rat and mouse TRβ1 sequences at the protein level, the mouse and rat TRβ2-specific N-terminal domains were less conserved, and the mouse protein was shorter by 39 amino acids at the N-terminus. Of the receptor species, only the mRNA encoding the TRβ2 isoform, which was restricted to thyrotropes, was decreased by T3 treatment, although the mRNA for the α2 variant was also reduced by T3 in thyrotropes and heart tissue. Levels of TRβ1 mRNA were not changed in liver, but were increased in thyrotropic tumors and also somewhat in brain, an organ that is not responsive to T3 by classical criteria
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