Human Reproduction Update Advance Access published online on October 19, 2008
Human Reproduction Update, doi:10.1093/humupd/dmn044
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Non-genomic progesterone actions in female reproduction
1 Endokrinologikum Hamburg, Falkenried 88, 20251 Hamburg, Germany 2 Institute for Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK
To whom correspondence should be addressed at: 3 Correspondence addresses: Tel: +49-40-47196591; Fax: +49-40-47196599; E-mail: gellersen{at}endokrinologikum.com (B.G.); Tel: +44-20-75942164; Fax: +44-20-75942183; E-mail: j.brosens{at}imperial.ac.uk (J.J.B.)
BACKGROUND: The steroid hormone progesterone is indispensable for mammalian procreation by controlling key female reproductive events that range from ovulation to implantation, maintenance of pregnancy and breast development. In addition to activating the progesterone receptors (PRs)-B and -A, members of the superfamily of ligand-dependent transcription factors, progesterone also elicits a variety of rapid signalling events independently of transcriptional or genomic regulation. This review covers our current knowledge on the mechanisms and relevance of non-genomic progesterone signalling in female reproduction.
METHODS: PubMed was searched up to August 2008 for papers on progesterone actions in ovary/breast/endometrium/myometrium/brain, focusing primarily on non-genomic signalling mechanisms.
RESULTS: Convergence and intertwining of rapid non-genomic events and the slower transcriptional actions critically determine the functional response to progesterone in the female reproductive system in a cell-type- and environment-specific manner. Several putative progesterone-binding moieties have been implicated in rapid signalling events, including the ‘classical’ PR and its variants, progesterone receptor membrane component 1, and the novel family of membrane progestin receptors. Progesterone and its metabolites have also been implicated in the allosteric regulation of several unrelated receptors, such as 
-aminobutyric acid type A, oxytocin and sigma1 receptors.
CONCLUSIONS: Identification of the mechanisms and receptors that relay rapid progesterone signalling is an area of research fraught with difficulties and controversy. More in-depth characterization of the putative receptors is required before the non-genomic progesterone pathway in normal and pathological reproductive function can be targeted for pharmacological intervention.
Key words: progesterone / reproduction / non-genomic / progesterone receptor / membrane progestin receptor
Received on August 11, 2008; revised September 8, 2008; accepted on September 11, 2008