Prostacyclin stimulates the adenylate cyclase system of human thyroid tissue

Abstract

Since Prostacyclin (PGI 2) is a major product of arachidonic acid metabolism in the human thyroid, we have studied the effects of PGI 2 on cAMP accumulation in human thyroid slices and cultured thyrocytes. In both systems, PGI 2 caused a dose- and time-dependent increase of cAMP accumulation with higher potency and efficacy than PGE 2. Two optically active isomers of 5,6-dihydro-PGI 2, i.e. stable synthetic analogs of PGI 2, had qualitatively similar effects to PGI 2. The relative potency ratio between the α- and β- isomer as well as their potency compared to PGI 2 were substantially similar to their potency in inhibiting human platelet aggregation. In thyroid slices, PGI 2 and its stable analogs had a greater than TSH in causing cAMP accumulation; however, in contrast to TSH, this effect was not associated with increased iodothyronine release except at maximal PGI 2 concentrations. TSH had no detectable effect on thyroidal PGI 2 synthesis and release. In cultured thyrocytes the effects of PGI 2 and its stable analogs were considerably less than those obtained with TSH and required higher concentrations. Such a discrepancy was not found in the case of PGE 2. These findings suggest the existence of a specific PGI 2-responsive adenylate cyclase system in human significance.