Beta 1 isoform-specific regulation of a triiodothyronine-induced gene during cerebellar development.
Although tissue-specific expression of the alpha 1 and beta 1 thyroid hormone receptors (TR-alpha 1 and TR-beta 1) suggests isoform-specific function, transfection studies to date have failed to show consistent differences in their ability to regulate gene expression. We here provide evidence that TR-beta 1 but not TR-alpha 1 regulates the expression of the gene coding for PCP-2 in cerebellar Purkinje cells during neonatal rat development and that such regulation appears to be both T3 dependent and T3 independent. Examination of neonatal rats revealed that the levels of three mRNAs expressed in cerebellar Purkinje cells (myoinositol-1,4,5-triphosphate receptor, calbindin, and PCP-2) rise from neonatal day 1 to day 15. This rise is preceded by the previously documented surge in brain T3 and TR-beta 1. Methimazole-induced hypothyroidism sharply reduces, but does not abolish, the rise in these mRNAs. Concomitant T3 administration normalizes the process. In order to establish more directly the role of TR-beta 1 and T3, cotransfection experiments were performed in CHO cells with PCP-2-lacZ construct and TR isoforms. These studies showed that TR-beta 1, even in the absence of T3, regulated the expression of the transfected PCP-2 construct. T3 augments the response to TR-beta 1 alone by 40% (P < .01). TR-alpha 1 had no effect on PCP-2-lacZ expression either in the presence or absence of T3.(ABSTRACT TRUNCATED AT 250 WORDS)
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D001483:Base Sequence; D016466:CHO Cells; D064026:Calbindins; D002460:Cell Line; D002531:Cerebellum / Q000254:growth & development* / Q000378:metabolism; D006224:Cricetinae; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis / Q000235:genetics; D014284:Triiodothyronine / Q000494:pharmacology*
D064026:Calbindins; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D064030:S100 Calcium Binding Protein G; D014284:Triiodothyronine