Semin Reprod Med 2007; 25(3): 178-186
DOI: 10.1055/s-2007-973430
Copyright © 2007 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Non-Genomic Sex Steroid Actions in the Vascular System

Xiao-Dong Fu1 , Tommaso Simoncini1
  • 1Molecular and Cellular Gynecological Endocrinology Laboratory, Department of Reproductive Medicine and Child Development, University of Pisa, Italy
Further Information

Publication History

Publication Date:
20 April 2007 (online)


Sex steroid receptors (SRs) traditionally have been regarded as transcription factors regulating the expression of target genes. However, alternative mechanisms of signal transduction have been identified recently. These actions of sex steroids do not require gene expression or protein synthesis and are independent of the nuclear localization of the receptors. Indeed, some of these actions are elicited by SRs at the plasma membrane. In the recent years significant advances have been made in the characterization of these rapid actions of sex steroids in the vascular system. Prototypical non-genomic actions of sex steroids at this level include the induction of rapid vasodilatation as well as anti-inflammatory and antiatherogenic actions. Ubiquitous signaling pathways traditionally believed to mediate the signals of growth factors or cytokines have been found to be recruited by sex steroid hormones via their receptors. These include tyrosine kinases, c-Src, G proteins, phosphatidylinositol 3-OH kinase/Akt, and mitogen-activated protein kinases. These cascades lead to rapid actions, such as the activation of nitric oxide synthesis, but are also critical for the regulation of the expression of several target genes in the nucleus, indicating a tight integration of the non-genomic and genomic pathways of sex steroid signaling. The understanding of the molecular basis of the non-genomic actions of sex steroids on the vascular system is important, and may become relevant for clinical purposes in the future.


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Tommaso SimonciniM.D. Ph.D. 

Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Reproductive Medicine and Child Development

Division of Obstetrics and Gynecology, University of Pisa, Via Roma, 57, 56100, Pisa, Italy