**7. References**


Moreover, data support a specific role for ERα on estradiol-stimulated prostacyclin production. Recently, selective ERα agonist 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1h-pyrazole (PPT), selective ERβ agonist (diarylpropionitril; DPN), and selective ERα antagonist, methylpiperidino-pyrazole (MPP), have become available (Krom *et al.*, 2007). With their use, it has been demonstrated that estradiol increased prostacyclin production, and COX-1 and prostacyclin synthase protein and gene expressions through ERα, whereas COX-2, phospholipases and thromboxane synthase expression remained unaltered (Sobrino *et al.*, 2010). The regulatory role of estradiol through ERα is supported by other studies. Estradiol increases levels of COX-1 in cerebral blood vessels from wild-type mice but was ineffective in ERα knockout mice (Geary *et al.*, 2001) and also increases COX-1 expression through ERα in ovine endothelial cells transfected with the human COX-1 promoter (Gibson *et al.*, 2005).

Remarkable progress has been made in elucidating the effects of estrogens on the vascular system, and the cellular and molecular mechanisms by which those effects are achieved. The analysis of published data supports estradiol increases prostacyclin vascular production in accordance with experimental and clinical research. This effect seems to be mediated mainly through ERα-dependent pathways which involve an increase in COX-1 and, in some cases, COX-2 activation and/or expression, and an augment in prostacyclin synthase expression, without affecting thromboxane A2 production. As a consequence, estradiol may reduce

Supported by the Spanish Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (grants FIS PI10/00518 and Red HERACLES RD06/0009/0005), Consellería de Sanidad

Abu-Taha, M., Rius, C., Hermenegildo, C., Noguera, I., Cerda-Nicolas, J.M., Issekutz, A.C.,

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**5. Conclusion** 

**6. Acknowledgments** 

1142-1150.

**7. References** 

(grants AP 117/2010 and GE 021/2010).


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**Part 10** 

**Factors Affecting Farrowing** 

