CONCENTRATION- AND TIME-DEPENDENT EFFECTS OF PROGESTERONE ON ENDOTHELIAL CELLS

Abstract

The termination of endogenous sex hormone release is thought to account for increases in cardiovascular disease (CVD) incidence in postmenopausal women. Thus, hormone replacement therapy may be a preventive measure against cardiovascular disease. To date, most research has been focused on estrogen treatment, but the effects of progesterone, a vasoactive hormone with effects on the endothelium, have received less attention. Two progesterone receptor subtypes, nuclear and membrane, are known to enact the effects of progesterone in endothelial cells which mediate the release of nitric oxide (NO). There is also some evidence that the two subtypes function in a coordinated manner. The aims of this thesis study are to assess the effects of different concentrations of progesterone on endothelial cells and isolate the actions of the progesterone receptor subtypes. Outcomes of this study include migration and proliferation assays to assess endothelial cell function and Western blotting to quantify endothelial nitric oxide synthase expression and phosphorylation. Progesterone and the membrane progesterone receptor agonist were found to inhibit migration and proliferation of human umbilical vein endothelial cells (HUVECs), while progesterone alone or in combination with the membrane progesterone receptor agonist increased endothelial nitric oxide synthase (eNOS) phosphorylation in HUVECs after 24 hours of incubation. While increased eNOS phosphorylation is thought to be beneficial to HUVEC function, other factors released in the presence of progesterone or progesterone receptor agonists may be scavenging bioavailable NO, thus reducing the angiogenic potential of HUVECs.