Expression of MAPkinases (Erk1/2) during decidualization in the rat: regulation by progesterone and nitric oxide.
The interaction between nitric oxide (NO), progesterone and the MAPkinase signalling pathway involved in decidualization was studied using immunohistochemistry during implantation in the rat. Early pregnant rats were treated with the inhibitor of nitric oxide synthesizing enzyme iNOS, aminoguanidine, either alone or in combination with the low dose antiprogestin, onapristone. The combined treatment was most effective on days 7 and 9 post coitum leading to a complete loss of embryos. The expression pattern of activated MAPkinases, Erk1/2 and iNOS appeared to be associated with the differentiation process of decidualization. A maximum staining of both enzymes was observed on day 9 post coitum in the mesometrial decidua. In addition, Erk1/2 and iNOS were highly coexpressed around the mesometrial sinusoids. Combined treatment with aminoguanidine and onapristone for 3 days led to a transient suppression of Erk1/2 and abolished Cox2 expression. Concomitantly, angiogenesis was reduced and dilated sinusoids were missing in the mesometrial decidua. In conclusion, our study suggests that (i) the member of the mitogen-activated protein kinase (MAPK) family, Erk1/2, is activated during implantation and may play an important role during the decidualization process, and (ii) this enzyme may be regulated by both progesterone and NO.
Thienel
T
T
Institute of Anatomy, University Hospital of Essen, Essen, Germany.
Chwalisz
K
K
Winterhager
E
E
D000818:Animals; D003656:Decidua / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006067:Gonanes / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011247:Pregnancy; D011256:Pregnancy Outcome; D011270:Pregnancy, Animal; D011374:Progesterone / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
D004791:Enzyme Inhibitors; D006067:Gonanes; D006146:Guanidines; D009569:Nitric Oxide; D011374:Progesterone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C053238:onapristone; C004479:pimagedine