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Mechanisms of Disease: new insights into the cellular and molecular pathology of Peyronie's disease

Nature Clinical Practice Urology volume 2, pages 291–297 (2005)Cite this article

Abstract

Peyronie's disease (PD) is characterized by fibrotic plaques in the penile tunica albuginea that cause curvature of the erect penis, and is often accompanied by pain and/or erectile dysfunction. This condition affects up to 9% of men. Treatment is mainly surgical, as pharmacologic therapy has limited efficacy. The pathophysiology of PD is poorly understood, but development of two rat models, extrapolation of what is known about the molecular pathology of other fibrotic conditions, and emphasis on the role of myofibroblasts and adult stem cells are helping to clarify etiology and identify new pharmacologic targets. Recent studies demonstrate a role for oxidative stress and cytokine release—primarily transforming-growth-factor β1—in development of PD fibrotic plaques. There is evidence indicating that these profibrotic factors interact with antifibrotic defense mechanisms, such as decrease of myofibroblast accumulation, elimination of reactive oxygen species by inducible nitric oxide synthase and neutralization of transforming-growth-factor β1 by decorin, such that some plaques are in dynamic turnover. Injury to the erect penis is thought to trigger PD by inducing extravasation of fibrin and subsequent synthesis of transforming-growth-factor β1. Despite the lack of statistical support for a causal association between trauma and PD, it is possible that undetected microtrauma is involved. It is not known whether ossification of PD plaques is linked to fibrosis progression or is a manifestation of an alternative pathway. Both processes seem to be related to activation of fibroblast/myofibroblast differentiation in the tunica albuginea and to osteogenic commitment of stem cells in this tissue.

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Figure 1: Normal wound healing following trauma or microtrauma to the penis does not lead to scar formation or fibrosis.
Figure 2: Peyronie's disease plaques result from dynamic interplay between profibrotic and antifibrotic factors in cells such as fibroblasts and myofibroblasts of the tunica albuginea.

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Acknowledgements

Experimental studies of the authors were funded by grants from the Eli and Edythe L Broad Foundation and NIH R01DK-53069, and partially by NIH Program grants G12RR-03026, and 5P20MD000545.

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Authors and Affiliations

  1. Adjunct Professor in the Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA

    Nestor F Gonzalez-Cadavid

  2. Professor in the Department of Urology, David Geffen School of Medicine at UCLA, and Chief of Urology, Harbor-UCLA Medical Center, Torrance, CA

    Jacob Rajfer

Authors
  1. Nestor F Gonzalez-Cadavid
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  2. Jacob Rajfer
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Corresponding author

Correspondence to Nestor F Gonzalez-Cadavid.

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The authors declare no competing financial interests.

Glossary

PENILE TUNICA ALBUGINEA

Dense white fibroelastic sheath enclosing the penile corpora cavernosa, lacunar smooth muscle and endothelium

DUPUYTREN'S DISEASE

A disease characterized by progressive thickening and contracture of fibrous tissue of the hand and fingers

MYOFIBROBLASTS

Differentiate from fibroblasts or stem cells; contain contractile arrays of smooth-muscle proteins (actin) that confer smooth-muscle-like phenotype; key cell in wound healing and fibrosis

PLASMINOGEN ACTIVATOR INHIBITOR 1 (PAI-1)

Inhibits activation of serine-protease-mediated conversion of plasminogen to plasmin, involved in clot lysis and tissue remodeling during wound healing; also inhibits metalloproteinases involved in collagen breakdown

SCLERODERMA

Skin progressively tightens and thickens due to deposition of fibrous connective tissue; internal organs can also be affected

SPINDLE

A microtubular array that regulates the distribution of chromosomes during meiosis and mitosis

PHOSPHODIESTERASE-5 (PDE5) INHIBITOR

An agent (sildenafil, vardenafil, tadalafil, and others) that inhibits PDE5, thus preventing breakdown of cGMP produced by activation of guanylyl cyclase by nitric oxide and other processes

PLEIOTROPIC

Producing multiple effects; that is, a single agent acting on several different processes

WESTERN BLOT

Proteins are fractionated by size on a gel, transferred to a membrane and immobilized to preserve their spatial arrangement; target proteins are identified by binding of specific antibodies and visualized by detection of colorimetric, autoradiographic, or chemiluminescent labels

REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION (RT-PCR)

Reverse transcriptase-catalyzed in vitro synthesis of a specific DNA fragment from an RNA template followed by generation of a large number of copies of the DNA

CD34

A 110kDa monomeric cell-surface antigen selectively expressed on human hematopoietic progenitor cells and other types of stem cells

ANEUSOMIES

Abnormal chromosome numbers; that is, too few or too many of one or more chromosomes in the nucleus

FLOW CYTOMETRY

Cells are sorted by size as they pass through a laser beam; those harboring an antigen of interest can be detected and counted by binding of an antibody conjugated to a fluorescent tag

S-PHASE

DNA is replicated during this phase of the cell cycle

TP53

Gene encoding a 53kDa tumor-suppressor protein; abnormalities of p53 are frequently detected in human tumors

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Gonzalez-Cadavid, N., Rajfer, J. Mechanisms of Disease: new insights into the cellular and molecular pathology of Peyronie's disease. Nat Rev Urol 2, 291–297 (2005). https://doi.org/10.1038/ncpuro0201

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