PGE2 Mediates the Progesterone Effects on the cAMP-Protein Kinase A Signaling Pathway in TT cells

Abstract

At near-term pregnancy, the levels of serum prostaglandin E2 (PGE2), calcitonin (CT) and progesterone (P4) are higher than non-pregnant levels. However, a cause and effect relationship between PGE2 and P4 on the activities of adenylyl cyclase (AC) and protein kinase A (PKA) have not been established. We used TT cell to study if PGE2 and P4 enhanced AC and PKA activities. TT cells were treated with P4 for 30 min and then PGE2, and the PGE2 receptors in media were measured. Also, TT cells were treated with P4, arachidonic acid (AA), NS398 and indomethacin (Indo). After treatments, the PGE2, AC activity, and PKA activity in media were measured. The results showed that P4 and AA increased PGE2 secretion, and those effects on P4 were in a dose-dependent manner. P4 up-regulated the levels of EP4 receptors, but NS398 blocked these effects. AC activities were increased with P4 by 2-fold, and with PGE2 by 3-fold. Also, treated with P4 + NS398, NS398 did not inhibit the P4 effect on AC activities in TT cells. In aspects of PKA activity, P4 and AA increased the activity of PKA in TT cells. Only treatment with PGE2 had no effect on the PKA activity, but PGE2 could enhance the P4 effects to 2.5-fold. NS398 and Indo blocked the effects of P4 and AA treatment on the PKA activities. These results suggested that PGE2 could enhance P4 effects, P4 may go through the PGE2 pathway to increase the activity of PKA in TT cells.