Progesterone increases nitric oxide synthesis in human vascular endothelial cells through activation of membrane progesterone receptor alpha (mPRα).

Progesterone increases nitric oxide synthesis in human vascular endothelial cells through activation of membrane progesterone receptor alpha (mPRα). Am J Physiol Endocrinol Metab. 2015 Mar 24;:ajpendo.00527.2014 Authors: Pang Y, Dong J, Thomas P Abstract Progesterone exerts beneficial effects on the human cardiovascular system by inducing rapid increases in nitric oxide (NO) production in vascular endothelial cells, but the receptors mediating these nongenomic progesterone actions remain unclear. Using human umbilical vein endothelial cells (HUVECs) as a model, we show that progesterone binds to plasma membranes of HUVECs with the characteristics of membrane progesterone receptors (mPRs). The selective mPR agonist, Org OD 02-0 had high binding affinity for the progesterone receptor on HUVEC membranes, whereas nuclear PR (nPR) agonists R5020 and medroxyprogesterone acetate displayed low binding affinities. Immunocytochemical and Western blot analyses confirmed that mPRs are expressed in HUVECs and are localized on their plasma membranes. NO levels increased rapidly after treatment with 20 nM progesterone, Org OD 02-0, and a progesterone-BSA conjugate, but not with R5020, suggesting this progesterone action is at the cell surface initiated through mPRs. Progesterone and Org OD 02-0 (20 nM) also significantly increased endothelial nitric oxide synthase (eNOS) activity and eNOS phosphorylation. Knock-down of mPRα expression by small in...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research