Aim: 

There is a little data regarding progestogens effects on prostanoid production, being one of them thromboxane A₂, a potent vasoconstrictor synthesized by two cyclooxygenases (COX-1 and COX-2). Postmenopausal women have an increased risk to develop cardiovascular pathologies. Our aim was to evaluate the effect of two clinically used progestogens: progesterone and medroxyprogesterone acetate (MPA), on thromboxane A₂ production by cultured human umbilical vein endothelial cells (HUVEC).

Methods: 

Cells were exposed to 1-100 nM of either progesterone or MPA, progesterone receptor antagonist (RU-486) was added to investigate the implication of these receptors, COX-1 selective inhibitor (SC-560) and COX-2 selective inhibitor (NS-398) were used to investigate both COX activities. Both COX-1 and COX-2, as well as thromboxane synthase mRNA expression were evaluated by quantitative real time PCR.

Results: 

Both progestogens at 10 and 100 nM significantly decreased thromboxane production and significantly increased mRNA expression of both COX, effects that were reversed by the use of RU-486. Nevertheless, thromboxane synthase mRNA did not significantly modify after the use of both progestogens. The use of SC-560 significantly reduced the thromboxane production even more than the NS-398.

Conclusions: 

Progesterone and MPA decreased thromboxane production by HUVEC in a progesterone receptor-dependent manner, mainly produced by an enhanced both COX-1 and COX-2 mRNA expression, and increased COX-1 activity, without changes in the thromboxane synthase mRNA expression.

Supported by Ministerio Ciencia e Innovación, ISCIII (FIS 06/0589, RED HERACLES RD06/0009), Consellería de Sanidad (AP 10/2007, AP 121/08) and Consellería de Educación, Generalitat Valenciana (GVPRE/2008/276). PJO holds a post-doc position, and AS is a FPI fellow (BFPI 06/145), both from Conselleria de Educación, Generalitat Valenciana, Spain.