Regulation of thyroid hormone receptor beta-2 mRNA levels by retinoic acid.
The thyroid hormone receptor, TR beta-2, whose expression is limited to the pituitary and parts of the central nervous system, is strongly negatively regulated at the pre-translational level by thyroid hormone (T3). We have investigated whether retinoic acid (RA), whose receptors (RARs) share a high degree of homology with the thyroid hormone receptors (TRs), can regulate this gene in a manner similar to T3, as has been shown for the growth hormone (GH) gene. GH3 cells were incubated with 10 nM T3, 1 microM RA or both for 48 h and then TR beta-2 mRNA levels determined by RNA blot hybridization analysis. We observed a 73% decrease in TR beta-2 mRNA levels after incubation with T3 and a two-fold increase in TR beta-2 mRNA levels after incubation with RA alone. In the presence of RA, the T3 effect on TR beta-2 mRNA levels was blunted with mRNA levels decreasing by only 20%. We investigated the mechanism by which retinoic acid increases and opposes the effects of T3 on levels of TR beta-2 mRNA. In transient transfection experiments using a reporter plasmid containing the TR beta-2 promoter and in nuclear run on assays, we found no effect of RA on TR beta-2 gene transcription. We then investigated whether the effects of RA were mediated at the post-transcriptional level. Determination of the apparent half-life of TR beta-2 mRNA using the transcriptional inhibitor, actinomycin D, showed that RA had no effect on TR beta-2 mRNA stability.(ABSTRACT TRUNCATED AT 250 WORDS)
Jones
K E
KE
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Yaffe
B M
BM
Chin
W W
WW
D000818:Animals; D002460:Cell Line; D003609:Dactinomycin / Q000494:pharmacology; D004355:Drug Stability; D005786:Gene Expression Regulation / Q000187:drug effects*; D006207:Half-Life; D009693:Nucleic Acid Hybridization; D010957:Plasmids; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology
D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D003609:Dactinomycin; D014212:Tretinoin