The interaction of signal transduction pathways in FRTL5 thyroid follicular cells: Studies with stable expression of beta 2-adrenergic receptors
- New England Medical Center Hospital, Boston, MA (USA)
Multiple signal transduction pathways interact in FRTL5 cells to promote thyroid follicular cell differentiated function and cell proliferation. In these cells, TSH is a tissue-specific mitogen that promotes DNA synthesis primarily through activation of adenylate cyclase. To further test the role of adenylate cyclase in regulating cell growth and differentiated function we have introduced into FRTL5 the human beta 2-adrenergic receptor (BAR) complementary DNA and have studied the ability of isoproterenol, alone and in combination with insulin-like growth factor I (IGF-I), to stimulate cAMP accumulation, iodide transport, (3H)thymidine incorporation into DNA, and cell growth. Wild-type FRTL5 were infected with a PLJ retroviral construct containing the BAR in either a sense (FRTL BAR) or antisense (FRTL RBAR) orientation, and cell populations were selected on the basis of resistance to the antibiotic geneticin. FRTL BAR expressed approximately 1.3 x 10(5) high affinity binding sites per cell for the beta 2-specific ligand, CGP-12177, while neither FRTL5 wild-type nor RBAR cells demonstrated any specific binding. FRTL BAR had significantly higher levels of intracellular cAMP, (3H)thymidine incorporation, and iodide uptake in the absence of added isoproterenol than FRTL RBAR or wild-type cells. In FRTL BAR, but not RBAR cells, isoproterenol stimulated a dose-dependent accumulation of cAMP, iodide uptake, (3H)thymidine incorporation, and cell growth. FRTL BAR and RBAR cells were equally responsive to TSH and to IGF-I. Isoproterenol enhanced the ability of IGF-I to stimulate (3H)thymidine incorporation in BAR but not RBAR cells. Isoproterenol partially inhibited the ability of TSH to stimulate cAMP generation and DNA synthesis.
- OSTI ID:
- 5924137
- Journal Information:
- Endocrinology; (USA), Vol. 128:3; ISSN 0013-7227
- Country of Publication:
- United States
- Language:
- English
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CYCLASES
BIOLOGICAL FUNCTIONS
SYMPATHOMIMETICS
RECEPTORS
THYROID CELLS
CELL PROLIFERATION
AMP
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL PATHWAYS
DNA
DNA REPLICATION
DOSE-RESPONSE RELATIONSHIPS
GROWTH FACTORS
IODIDES
LIGANDS
MAN
MEMBRANE TRANSPORT
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TSH
ANIMAL CELLS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
DRUGS
ENZYMES
FUNCTIONS
HALIDES
HALOGEN COMPOUNDS
HETEROCYCLIC COMPOUNDS
HORMONES
HYDROGEN COMPOUNDS
IODINE COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LYASES
MAMMALS
MEMBRANE PROTEINS
MITOGENS
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDE HORMONES
PITUITARY HORMONES
PRIMATES
PROTEINS
PYRIMIDINES
REACTION KINETICS
RIBOSIDES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques