The relation between adenylate cyclase activation and camp accumulation in the horse thyroid gland stimulated by thyrotropin

Abstract

The concentration-response relationships for TSH and plasma membrane adenylate cyclase activity and for TSH and cAMP levels in slices have been compared in horse thyroids: the curves exhibited striking differences. Several models of cAMP metabolism are shown not to account for these discrepancies: notably the existence of one phosphodiesterase or the hypothesis of cAMP sequestration in the cell. However, the existence of two cAMP phosphodiesterases with K m in the 10 −6 M and 10 −3 M ranges allows a good fitting of the experimental date. It is shown that the presence of such phosphodiesterases provides the cell with a powerful amplification device. By comparing the theoretical values with those which could eventually be measured, it would be possible to check if the plasma membrane adenylate cyclase assay is a good experimental model for the enzyme in vivo and to test the hypothesis that the major part of cellular cAMP is in a free form.