Prostaglandin E2, cAMP and cAMP-dependent protein kinase isozymes during decidualization of rat endometrial stromal cells in vitro.
When endometrial stromal cells from rat uteri sensitized for the decidual cell reaction are cultured in vitro, they undergo decidualization, as indicated by increased alkaline phosphatase (ALP) activity. Prostaglandin E2 (PGE2) stimulates this increase in activity. To determine the role of cAMP in the stimulation, we examined the effect of 2':5'-dideoxyadenosine (DDA), an inhibitor of adenylate cyclase, on the ability of PGE2 to increase ALP activity. As indicated by [3H]cAMP accumulation in endometrial stromal cells preincubated with [3H]adenine, DDA inhibited PGE2-stimulated synthesis of cAMP in a concentration-dependent manner. Furthermore, DDA caused a significant decrease in the PGE2-induced ALP activity on day 3 of culture. Dibutyryl cAMP overrode this inhibition. The effect of DDA was not mimicked by adenosine, which had a stimulatory effect on ALP activity in the non-stimulated cultures and no significant effect in PGE2-stimulated cultures. Thus the inhibitory effect of DDA on PGE2-stimulated ALP activity is unlikely to be mediated by adenosine-related receptors. These results suggest that cAMP is an essential, but not necessarily the only, intracellular messenger of PGE2 in endometrial stromal cells during decidualization. The isozymes of cAMP-dependent protein kinase (PKA) mediating the effect of cAMP were assessed by using cAMP analogues directed at selective sites of PKA isozymes. Synergistic activation of ALP activity in endometrial stromal cells by pairs of analogues directed at types I and II PKA suggested that both types were functionally important during decidualization.
Yee
G M
GM
Department of Physiology, University of Western Ontario, London, Canada.
Kennedy
T G
TG
D000241:Adenosine / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology*; D003656:Decidua / Q000166:cytology* / Q000502:physiology; D016048:Dideoxyadenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D004717:Endometrium / Q000166:cytology*; D005260:Female; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000067956:Adenylyl Cyclase Inhibitors; D007527:Isoenzymes; D016048:Dideoxyadenosine; D003994:Bucladesine; C021008:2',5'-dideoxyadenosine; D000242:Cyclic AMP; D011494:Protein Kinases; D000469:Alkaline Phosphatase; D000241:Adenosine; D015232:Dinoprostone