Cloning, chromosomal assignment, and regulation of the rat thyrotropin receptor: Expression of the gene is regulated by thyrotropin, agents that increase cAMP levels, and thyroid autoantibodies

Journal Article · Wed Aug 01 04:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.15.5677· OSTI ID:5988567

Akamizu, Takashi; Ikuyama, Shoichiro; Saji, Motoyasu; Kosugi, Shinji; Kozak, C; McBride, O W; Kohn, L D ^[1]

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1. National Institutes of Health, Bethesda, MD (USA)

A rat thyrotropin (thyroid-stimulating hormone, TSH) receptor cDNA was isolated that encoded a protein of 764 amino acids, M{sub r} 86,528. Transfection of the cDNA caused COS-7 cells to develop a TSH-sensitive adenylate cyclase response and the ability to bind {sup 125}I-labeled TSH; both activities were similar to those of rat FRTL-5 thyroid cells and not duplicated by lutropin. The gene represented by the cDNA was assigned to mouse chromosome 12 and human chromosome 14. Northern analyses identified two species of mRNA, 5.6 and 3.3 kilobases, in FRTL-5 thyroid cells; the transcripts appeared to differ only in the extent of their 3{prime} noncoding sequences. There were minimal amounts of the two mRNAs in rat ovary, and neither was detected in RNA preparations from rat testis, liver, lung, brain, spleen, and FRT thyroid cells, which do not have a functional TSH receptor. TSH decreased both mRNA species 3- to 4-fold within 8 hr in FRTL-5 thyroid cells; down-regulation was dependent on TSH concentration and duplicated by forskolin, cholera toxin, or 8-bromo-cAMP but not by a phorbol ester. Down-regulation was also duplicated by throid-stimulating autoantibodies, which increased cAMP levels, but not by thyrotropin binding-inhibiting autoantibodies, which actually increased TSH receptor mRNA levels.

• OSTI ID: 5988567
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:15; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACID SEQUENCE
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
CHROMOSOMES
CLONING
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DNA
DNA HYBRIDIZATION
DNA POLYMERASES
DNA SEQUENCING
DNA-CLONING
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
FIBROBLASTS
GENE REGULATION
GENETIC MAPPING
HETEROCHROMOSOMES
HORMONES
HYBRIDIZATION
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
MAN
MAPPING
MEMBRANE PROTEINS
MOLECULAR STRUCTURE
NUCLEI
NUCLEIC ACIDS
NUCLEOTIDYLTRANSFERASES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PEPTIDE HORMONES
PHOSPHORUS-GROUP TRANSFERASES
PITUITARY HORMONES
POLYMERASES
PRIMATES
PROTEINS
RADIOISOTOPES
RADIORECEPTOR ASSAY
RECEPTORS
RECOMBINANT DNA
SOMATIC CELLS
STRUCTURAL CHEMICAL ANALYSIS
TRACER TECHNIQUES
TRANSCRIPTION
TRANSFERASES
TSH
VERTEBRATES