In vitro effects of progesterone and progestins on vascular cells.

The impact of progesterone on the cardiovascular system is relevant, but not as well characterized as the effects of estrogens. The recent early interruption of the conjugated equine estrogens (CEE)-medroxyprogesterone acetate (MPA) arm of the Women's Health Initiative trial, but not of the parallel CEE-only treatment arm, suggesting the possibility of harmful cardiovascular effects of the progestins, boosts the debate on the role of progesterone and progestins on the vascular tree. The data available up to now show the presence of important regulatory effects of progestagens on vascular cells. Additionally, the presence of a progestagen results in diverse modifications of the effects of estrogens, sometimes acting synergically, others being neutral or antagonizing estrogens' effects. Notwithstanding the availability of consistent observations on the functional effects of progestins on the cardiovascular system, the molecular mechanisms of progestins actions on vascular cells have been up to now only scarcely characterized. Novel mechanisms of signal transduction are being discovered for progesterone receptors in different tissues, some of which are independent of gene transcription regulation, and are therefore indicated as "nongenomic." Furthermore, the contribution to signal transduction of co-activators is currently widely investigated, in order to understand the ways to tissue-specificity and to engineer new progesterone receptor modulators. The understanding of the molecular basis of progesterone receptor signaling in vascular tissue is therefore of paramount importance for the development of hormonal agents with an optimal cardiovascular profile.