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Mol. Hum. Reprod. Advance Access published online on December 10, 2004
Molecular Human Reproduction, doi:10.1093/molehr/gah138
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Molecular Human Reproduction © European Society of Human Reproduction and Embryology 2004; all rights reserved
Received September 27, 2004
Revised November 12, 2004
Accepted November 17, 2004

Article

Identification, characterization and biological activity of oxytocin receptor in the developing human penis

Linda Vignozzi 1, Gabriella Barbara Vannelli 2, Annamaria Morelli 1, Rosa Mancina 1, Mirca Marini 2, Pietro Ferruzzi 1, Clara Crescioli 1, Michaela Luconi 1, Silvia Donati 1, Alessandra Daphne Fisher 1, Elisabetta Baldi 1, Sandra Filippi 3, Gianni Forti 1, and Mario Maggi 1*

1 Department of Clinical Physiopathology, Andrology and Endocrinology Unit, Florence, Italy
2 Department of Anatomy, Histology and Forensic Medicine, Florence, Italy
3 Department of Pharmacology and Clinical Physiopathology, Interdepartmental Laboratory of Functional and Cellular Pharmacology of Reproduction, University of Florence, 50139 Florence, Italy

* To whom correspondence should be addressed.
Mario Maggi, E-mail: m.maggi{at}dfc.unifi.it


  Abstract

Although abnormalities of the male external genitalia (MEG) are a relatively common problem, little is known concerning the molecular mechanisms that finely regulate penile development. We report here the expression of the oxytocin receptor (OTR) gene by real-time RT-PCR in human fetal tissues (11th-12th week of gestation), including the MEG. The developing penis expressed a very high level of OTR mRNA, only a half log10 unit lower than fetal central nervous system, used as a positive control. The OTR protein is also highly expressed (western, immunohistochemistry and binding studies) and immunolocalized both in the mesenchymal body and in the surrounding blood capillaries, which will later constitute penile trabeculae and sinusoids. Binding studies using [125I]oxytocin antagonist ([125I]OTA) in cultured human fetal penile smooth muscle cells (hfPSMC) revealed the presence of specific OTR with a high capacity and affinity for oxytocin (OT) and for OTA. Increasing concentrations of OT dose-dependently induced intracellular Ca2+ mobilization. Furthermore, OTR mediated an increase in the proliferation and the migration of hfPSMC. In conclusion, we demonstrate that in the developing human MEG, OTR is highly expressed and might be involved in coordinating timely and appropriate proliferation and migration of the penile cells. Thus, OTR might represent an additional target for investigating human fetal MEG organogenesis.

Keywords: development; oxytocin receptor; penis; smooth muscle cell.
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