title: The positive regulation of human thyrotropin (TSH) receptor messenger ribonucleic acid by recombinant human TSH is at the intranuclear level.
abstract: 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.
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.
authors.forename: G K
authors.initials: GK
authors.lastname: Huber
authors.forename: S P
authors.initials: SP
authors.lastname: Weinstein
authors.forename: P N
authors.initials: PN
authors.lastname: Graves
authors.forename: T F
authors.initials: TF
authors.lastname: Davies
mesh_terms: 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*
chemical_list: 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