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Expression and Distribution of Phosphodiesterase Isoenzymes in the Human Seminal Vesicles

Authors

  • Stefan Ückert PhD,

    Corresponding author
    1. Department of Urology and Urological Oncology, Hannover Medical School, Division of Surgery, Hannover, Germany
    2. Institute for Biochemical Research and Analysis, Sexual Function Research Unit, Medical Park Business Area, Hannover, Germany
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  • Eginhard S. Waldkirch MD, PhD,

    1. Department of Urology and Urological Oncology, Hannover Medical School, Division of Surgery, Hannover, Germany
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  • Joachim E. Sonnenberg PhD,

    1. Institute for Biochemical Research and Analysis, Sexual Function Research Unit, Medical Park Business Area, Hannover, Germany
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  • Peter Sandner PhD,

    1. Department of Cardiovascular Research, Bayer-Schering Pharma AG, Bayer HealthCare AG, Pharma Research Center, Wuppertal, Germany
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  • Markus A. Kuczyk MD, PhD,

    1. Department of Urology and Urological Oncology, Hannover Medical School, Division of Surgery, Hannover, Germany
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  • Petter Hedlund MD, PhD

    1. Department of Urology, University Vita Salute, San Raffaele Hospital, Urological Research Institute, Milan, Italy
    2. Department of Clinical and Experimental Pharmacology, Lund University Hospital, Institute for Laboratory Medicine, Lund, Sweden
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Stefan Ückert, PhD, Department of Urology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover, 30625, Germany. Tel: (49) 511 5 32 34 37; Fax: (49) 511 5 32 84 37; E-mail: sue_de_99@yahoo.de

ABSTRACT

Introduction.  Phosphodiesterase (PDE) isoenzymes have been shown to play a role in the control of human male genital tissues. There are hints from basic research and clinical studies that PDE5 inhibitors may have the ability to retard the male ejaculatory response. While the expression of PDE isoenzymes in the human seminal vesicles (SVs) has been described, the distribution of cyclic adenosine monophosphate (AMP)- and cyclic guanosine monophosphate (GMP)-PDEs has not yet been investigated.

Aim.  The aim of this study was to elucidate the expression and distribution of PDE isoenzymes PDE3A, PDE4 (isoforms A and B), PDE5A, and PDE11A in human SV tissue.

Methods.  Using immunohistochemistry (double-labeling techniques, laser fluorescence microscopy), the occurrence of PDE3A, PDE4A, PDE4B, PDE5A, and PDE11A, the vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), and protein gene product 9.5 (PGP 9.5) was examined in sections of SV. Cytosolic supernatants prepared from isolated human SV tissue were subjected to Western blot analysis using specific anti-PDE antibodies.

Main Outcome Measure.  The expression and distribution by of PDE3A, PDE4A, PDE4B, PDE5A, and PDE11A in the human SV were investigated by means of immunohistochemistry and Western blot analysis.

Results.  Immunosignals specific for PDE3A were seen in both the smooth muscle and the glandular epithelium, whereas staining for PDE4A, PDE5A, and PDE11A was mainly limited to epithelial cells. Varicose nerve fibers transversing the sections also presented staining for PDE3A. In nerve fibers and nerve endings, PDE4A and PDE4B were found co-localized with VIP; PDE5A-positive nerves also presented immunosignals specific for CGRP. The expression of said PDE isoenzymes was confirmed by Western blotting.

Conclusions.  The results indicate that cyclic AMP- and cyclic GMP-PDE isoenzymes are involved in the control of secretory activity and efferent neurotransmission in the SV. These findings might be of importance with regard to the identification of new therapeutic avenues to treat premature ejaculation. Ückert S, Waldkirch ES, Sonnenberg JE, Sandner P, Kuczyk MA, and Hedlund P. Expression and distribution of phosphodiesterase (PDE) isoenzymes in the human seminal vesicles. J Sex Med 2011;8:3058–3065.

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