Biochemical action of medroxyprogesterone acetate on ovariectomized obese rats

Abstract

Obesity, cardiovascular and bone diseases are multifactorial clinical entities that often coexist in postmenopausal women. Medroxyprogesterone acetate (MPA) is usually employed in hormone replacement therapy. Previous studies carried out in our laboratory at vascular level, demonstrated a divergent action between native progesterone (Pg) and its synthetic analogue MPA, evidenced by an oxidative, proatherogenic and prothrombotic effect, and an impairment in aortic recovery elicited by MPA in contrast to Pg action. VEGF is a key mediator in vascular and bone repair. The aim of this work was to evaluate the effect of MPA on VEGF production on vascular and bone tissue, as wells as the impact on adiposity oxidative stress in a model of obesity and hypoestrogenism. To that end, aortic endothelial cells (EC), retroperitoneal adipose tissue (AT) and femoral diaphysis (FD) were isolated from ovariectomized Wistar rats fed with a high-fat diet (27%) for 10 weeks. For in vitro treatments, AT explants, FD and EC cultures were incubated with 10 nM MPA for 20 h. Control group received vehicle only (isopropanol). Treatment of EC culture with MPA induced a significant reduction in VEGF synthesis (34% vs control, P<0.0001, ELISA Kit). This inhibition of growth factor synthesis was also observed in FD after exposure to the synthetic progestin (33% vs control, P<0.01). Both results suggest an impair action on tissue repair capability. When AT was incubated with MPA, reduction in oxidative stress was detected. Significant decrease in H2O2 release from AT isolated form obese rats was observed (2725 ± 432 vs 2043 ± 69 nmol H2O2/g of tissue, control vs MPA respectively, P<0.05, fluorometric assay). In addition, after treatment of AT with MPA, leptin levels increased in the culture medium (28% vs control, P<0.025, ELISA kit). The results presented suggest that, under hypoestrogenism and obesity, MPA could exert negative or positive effects according to the target tissue involved.