The Relationship of Growth and Adenylate Cyclase Activity in Cultured Thyroid Cells: Separate Bioeffects of Thyrotropin

Using a clonal line of TSH-dependent functional rat thyroid cells, the effects of TSH on cAMP production and cell growth, as measured by cell number and [14C]thymidine incorporation, were compared. The withdrawal of TSH from the medium stopped the growth of cells, as measured by cell number. After 24 h in TSH-free medium, an acute challenge with 1 × 10-11 M pure TSH caused a 40-fold increase in the cAMP level; this response increased to greater than 80-fold as TSH withdrawal from the culture system was prolonged over 10 days. In contrast to these acute effects on cAMP levels, an increase in [14C]thymidine incorporation required 20-fold higher TSH concentrations and waned to an unresponsive level after 10 days of TSH withdrawal. After withdrawal of TSH from the medium for 10 days, readdition of TSH could return cell growth to normal rates only after a 2-day lag period. In terms of the lag, the TSH effect on cell number was paralleled by its effect on thymidine incorporation, not cAMP levels; (Bu)2-cAMP at ...