P H CUTINI and others Progestins and vascular function 220:3 179–193 Research Differential regulation of endothelium behavior by progesterone and medroxyprogesterone acetate Pablo H Cutini1,2, Adria´n E Campelo1,2 and Virginia L Massheimer1,2 Correspondence should be addressed 1Ca´ tedra de Bioquı´mica Clı´nica II, Departamento de Biologı´a, Bioquı´mica y Farmacia, Universidad Nacional to V L Massheimer del Sur (UNS), San Juan 670, B8000ICN, Bahı´a Blanca, Argentina Email 2Consejo Nacional de Investigaciones Cientı´ficas y Te´ cnicas (CONICET), Argentina, Buenos Aires, Argentina
[email protected] Abstract Medroxyprogesterone acetate (MPA) is a synthetic progestin commonly used in hormone Key Words replacement therapy (HRT). The aim of this research was to study and compare the effect of " cell migration progesterone (Pg) and MPA on the regulation of cellular events associated with vascular " medroxyprogesterone homeostasis and disease. Platelet adhesion to endothelial cells (ECs), nitric oxide (NO) acetate production, and cell migration were studied using murine ECs in vitro exposed to the " nitric oxide progestins. After 7 min of treatment, MPA significantly inhibited NO synthesis with respect " progesterone to control values; meanwhile, Pg markedly increased vasoactive production. In senile ECs, " vascular tissue the stimulatory action of Pg decreases; meanwhile, MPA maintained its ability to inhibit Journal of Endocrinology NO synthesis. The presence of RU486 antagonized the action of each steroid. When ECs were preincubated with PD98059 (MAPK inhibitor) or chelerythrine (protein kinase C (PKC) inhibitor) before Pg or MPA treatment, the former totally suppressed the steroid action, but the PKC antagonist did not affect NO production.