The positive regulation of human thyrotropin (TSH) receptor messenger ribonucleic acid by recombinant human TSH is at the intranuclear level.
We have assessed the regulatory influence of human recombinant TSH (rec-hTSH) on its homologous receptor (TSHR) using a well characterized human fetal thyroid monolayer cell culture technique. Under the culture conditions employed, fetal human thyroid cells showed basal expression of TSHR-specific mRNA transcripts, and the addition of rec-hTSH (1 U/L) induced up to an 8-fold increase in specific mRNA over a 48-h observation period. This induction was simulated by bromo-cAMP in a dose-dependent manner, indicating that the stimulatory effect of rec-hTSH was active at the postreceptor level. Furthermore, there was no detectable increase in the transcription rate of the TSHR gene after stimulation with rec-hTSH for 12-36 h, although a marked increase in thyroglobulin-specific mRNA was observed. Rec-hTSH also had no influence on the half-life of TSHR-specific mRNA, which remained at approximately 16 h in the presence or absence of rec-hTSH. These data indicate that rec-hTSH induced up-regulation in human thyroid cell TSHR-specific mRNA and that the mechanism of this regulation was likely to be secondary to a posttranscriptional nuclear event involving changes in the regulation of primary unspliced mRNA for the TSHR.
Huber
G K
GK
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
Weinstein
S P
SP
Graves
P N
PN
Davies
T F
TF
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000022:Abortion, Spontaneous; D000704:Analysis of Variance; D001483:Base Sequence; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D005260:Female; D005333:Fetus; D005786:Gene Expression Regulation / Q000187:drug effects*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000235:genetics*; D011994:Recombinant Proteins / Q000494:pharmacology; D013961:Thyroid Gland / Q000187:drug effects / Q000502:physiology*; D013972:Thyrotropin / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D009004:Monosaccharide Transport Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; D011994:Recombinant Proteins; D003609:Dactinomycin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013972:Thyrotropin; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases