Thyroid hormones transcriptionally regulate the beta 1-adrenergic receptor gene in cultured ventricular myocytes.
Exposure of ventricular myocytes in primary culture to triiodothyronine (T3) increased the number of beta 1-adrenergic receptors per cell by 2.1 +/- 0.3-fold (n = 7) within 48 h. Immunoblots of membranes prepared from myocytes revealed a marked increase by T3 in the 64-kDa species of the beta 1-adrenergic receptor. Steady-state levels of beta 1- and beta 2-adrenergic receptor mRNAs quantified by DNA-excess solution hybridization were 0.26 +/- 0.06 and 0.81 +/- 0.05 amol of beta-adrenergic receptor mRNA/micrograms of total cellular RNA, respectively (n = 4). beta 1-Adrenergic receptor mRNA increased to 0.90 +/- 0.07 amol/micrograms RNA by 2-4 h after exposure to T3 and then declined by 6 h to twice that of control cells. beta 2-Adrenergic receptor mRNA levels were unaffected by T3. Northern blot hybridization also showed a rapid and sustained increase of 2.2 +/- 0.4-fold (n = 4) in beta 1-adrenergic receptor mRNA. The rate of beta 1-adrenergic receptor gene transcription assessed by nuclear run-on transcription assays increased by 3.4 +/- 0.4-fold in cells treated for 30 min with T3. Ventricular cells contained nuclear T3 receptors and mRNAs of c-erbA genes that encode T3 binding proteins. These studies indicate that thyroid hormones regulate the cardiac beta-adrenergic receptor-adenylate cyclase system by controlling the rate of transcription of the beta 1-adrenergic receptor gene. This regulation involves nuclear T3 receptors and appears to be exerted in a tissue-specific manner.
Bahouth
S W
SW
Department of Pharmacology, College of Medicine, University of Tennessee, Memphis 38163.
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D008969:Molecular Sequence Data; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D011988:Receptors, Thyroid Hormone; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000502:physiology*
D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D004247:DNA