Studies on the mechanism of desensitization of the cyclic AMP response to TSH stimulation in a cloned rat thyroid cell line.
We examined aspects of the mechanism of desensitization of adenylate cyclase activation by TSH in a cloned line of rat thyroid cells (FRTL). Increasing FRTL intracellular cAMP concentrations by preincubation for 6 h in either 1 mM dBcAMP or 100 microM forskolin did not induce TSH desensitization. Forskolin stimulation was unimpaired in TSH-desensitized cells, indicating 'uncoupling' of the adenylate cyclase catalytic unit from the TSH receptor. Stimulation by the Ni inhibitory pathway of the adenylate cyclase by epinephrine (10(-6) M-10(-4) M in the presence of 10(-4) M propranolol) was unaltered in cells previously desensitized to TSH. That is, Ni-mediated inhibition of adenylate cyclase was additive to TSH desensitization. Pre-exposure of FRTL cells for 18 h to 50 ng/ml pertussis toxin did not prevent the induction of TSH desensitization. TSH desensitization was prevented by cycloheximide or actinomycin D added during the last 3-4 h of a 6 h period of TSH stimulation. The rates of turnover of the putative desensitization protein and its mRNA therefore appear to be similar.
H
H
Hirayu
R P
RP
Magnusson
B
B
Rapoport
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000378:metabolism*; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology*; D011989:Receptors, Thyrotropin; D013961:Thyroid Gland / Q000166:cytology / Q000502:physiology*; D013972:Thyrotropin / Q000502:physiology*
D011956:Receptors, Cell Surface; D011989:Receptors, Thyrotropin; D012313:RNA; D013972:Thyrotropin; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases