Cross-talk between rapid and long term effects of progesterone on vascular tissue.
We tested the hypothesis whether; the non-genomic action of progesterone (Pg) on vascular tissue would be associated with hormonal long term effect on the modulation of cell growth. Using rat aortic strips, we showed that the stimulatory effect of Pg on nitric oxide synthesis involved both kinase and phosphatase pathways. The increase in the vasoactive production was prevented by the MAPK inhibitor (PD98059). In addition, preincubation with a phosphatase antagonist potentiated the hormonal effect. Pg increased PKC activity, but the inhibition of PKC did not alter the stimulatory action of the hormone on nitric oxide generation. In endothelial cell cultures (EC), 24h treatment with Pg significantly diminished cell proliferation. This antiproliferative effect was suppressed by the PKC inhibitor chelerythrine (chel) and l-NAME (nitric oxide synthase inhibitor). We also observed that Pg stimulates EC migration. In summary, the present findings provide evidence of an integration of genomic and non-genomic effects in the mechanism of action displayed by Pg in vascular tissue. The fast effects elicited by the hormone implies signal transduction activation required for the regulation of vasoactive production, but also necessary for the modulation of endothelial cells growth.
Cutini
Pablo
P
Cátedra de Bioquímica Clínica II, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan, Bahía Blanca, Argentina.
Sellés
Juana
J
Massheimer
Virginia
V
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
D009569:Nitric Oxide; D011374:Progesterone; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C