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 Table of Contents  
ORIGINAL ARTICLE
Year : 2013  |  Volume : 33  |  Issue : 1  |  Page : 28-31

Evaluation of plasma-transforming growth factor-β1 in active-phase Peyronie’s disease


1 Department of Dermatology, Venerology and Andrology, Al-Azhar University for Boys, Cairo, Egypt
2 Department of Clinical Pathology, Al-Azhar University for Girls, Cairo, Egypt

Date of Submission01-Mar-2013
Date of Acceptance10-Apr-2013
Date of Web Publication23-Jun-2014

Correspondence Address:
Mohamed I. Kamel
MD, Department of Dermatology, Venerology and Andrology, Al-Azhar University for Boys, 115 Manial street, PO Box 44555, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.7123/01.EJDV.0000431535.86674.97

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  Abstract 

Background

Peyronie’s disease (PD) is an acquired disorder of the penile tunica albuginea. PD may manifest in the form of palpable penile plaques, penile curvature, erectile dysfunction, and/or painful erections, all of which carry significant morbidity and psychological distress for both patients and partners. The underlying etiopathogenesis of PD is not well understood but is thought to be caused by injury to the penis, usually through sexual activity. The study of transforming growth factor-β (TGF-β) is of particular interest in the identification of the pathophysiological mechanisms involved in PD tunical fibroses and in the activation of inflammatory cytokines and fibrosis-associated cytokines.

Aim

The aim of the study was to determine and evaluate the plasma TGF-β1 level in patients with active-phase PD compared with control individuals and determine the association between TGF-β1 level and disease activity.

Methods

The study was carried out on 30 patients with clinically suspected and ultrasonographically confirmed PD, and the results were compared with 20 matched healthy individuals who formed the control group. All participants were subjected to full history taking, clinical examination, ultrasonographic evaluation, and measurement of plasma TGF-β1 levels.

Results

A significant increase in plasma TGF-β1 levels was found in active-phase PD patients when compared with controls, especially in patients suffering from pain and deformity and patients with associated comorbidities such as diabetes or hypertension (P<0.05).

Conclusions

Assessment of plasma TGF-β1 levels from peripheral blood samples is a simple method for detecting cavernous TGF-β1 expression without the need for penile blood samples. TGF-β1 may be a marker for PD.

Keywords: diabetes, hypertension, Peyronie’s disease, plasma TGF-β1


How to cite this article:
Elzorkany MI, Ahmed NA, Kamel MI, Hussein NR, Embarak MM. Evaluation of plasma-transforming growth factor-β1 in active-phase Peyronie’s disease. Egypt J Dermatol Venerol 2013;33:28-31

How to cite this URL:
Elzorkany MI, Ahmed NA, Kamel MI, Hussein NR, Embarak MM. Evaluation of plasma-transforming growth factor-β1 in active-phase Peyronie’s disease. Egypt J Dermatol Venerol [serial online] 2013 [cited 2019 Sep 15];33:28-31. Available from: http://www.ejdv.eg.net/text.asp?2013/33/1/28/135111


  Introduction Top


Peyronie’s disease (PD) is an acquired disorder of penile tunica albuginea that affects ∼4–9% of men in the general population and causes significant morbidity and psychological distress for both patients and their partners 1.

Current understanding of the natural history of the disease divides PD patients into those with an active phase and those with a mature or stable phase. The active phase of the disease is associated with painful erections and changing size of the penile plaque and may be associated with penile curvature and/or erectile dysfunction. The stable phase of PD is associated with painless, stable penile curvatures, in many instances leading to development or progression of erectile dysfunction 2. The underlying etiopathogenesis of PD is not well understood but is thought to be caused by injury to the penis usually through sexual activity, although many patients are often unaware of any traumatic event or injury 3.

Inflammation and alteration of the collagen metabolism have been proposed as possible causes of the etiopathogenesis of PD because of the detection of a significant increase in collagen fibers in PD pathology 4. Transforming growth factor-β (TGF-β) is a member of a family of dimeric polypeptide growth factors. There are three isoforms of TGF-β expressed in mammals: TGF-β1, TGF-β2, and TGF-β3 5. Ryu et al. 6 identified a significant role for TGF-β1 as a fibrogenic cytokine that induces fibrosis in a variety of organs. TGF-β1 has been suggested to have an important role in cavernous fibrosis and resultant erectile dysfunction 7.


  Patients and methods Top


Patients

The current study included 30 patients suffering from active-phase PD. They were selected from among patients attending the andrology clinics of Al-Azhar University hospital between November 2011 and June 2012. Their ages ranged from 26 to 63 years (mean±SD=44.4±10.4). Twenty age-matched healthy individuals served as controls. The study was approved by department of dermatology, venereology review board, Al-Azhar University for girls Cairo, Egypt.

All studied patients were categorized as having active-phase PD. All patients with a palpable painful penile plaque with or without penile deviation who had a disease duration of not more than 6 months and had not received any treatment for their condition were included in the study. All patients with severe infectious diseases or known systemic illness that may alter the TGF-β1 level, such as keloid, glomerulonephritis, pulmonary fibrosis, liver fibrosis, or internal malignancy, were excluded from the study. Informed consent was obtained from all studied patients and healthy control volunteers before enrollment in the study.

Methods

All patients enrolled in the study underwent a detailed history taking, including age, duration of the disease, occupation, special habits (as smoking), and previous treatment attempts. A thorough clinical examination was performed on all patients and included a general examination especially for the hands and feet to determine the presence of Dupuytren’s contracture and plantar fasciitis, respectively. A genital examination was also performed for the presence of visible scars and penile deformity, including palpation for the size and consistency of the penile plaque and monitoring of tenderness.

A penile ultrasonography was performed for all patients for determination of the site and size of the penile plaque 8; the instrument used was Esauti AU5 (Esaote Group, Genova, Italy), a colored duplex ultrasound machine with a 10 MHz linear probe.

Plasma TGF-β1 levels were measured using a DRG TGF-β1 kit (DRG International Inc., Mountain Avenue, Springfield, New Jersey, USA), which is a solid-phase sandwich enzyme linked immuosorbent assay (ELISA). A monoclonal antibody specific for TGF-β1 had been coated onto the wells of the microtiter strips provided. Samples, including standards of known TGF-β1 content, control specimens, and plasma from the studied groups, were pipetted into these wells, followed by the addition of a biotinylated secondary antibody. During the first incubation, the TGF-β1 antibody bound simultaneously to the immobilized antibody on one site and to the solution-phase biotinylated antibody on a second antibody on a second site. After removal of excess antibody, the streptavidin–peroxidase enzyme was added. This binds to the biotinylated antibody to form an immune enzyme sandwich complex. After a second incubation, followed by washing to remove the entire unbound enzyme, a substrate solution was added, which was acted upon by the bound enzyme to produce color. The intensity of this colored product was directly proportional to the concentration of TGF-β1 present in the original specimens.

The collected data were organized, tabulated, and statistically analyzed using Epi Info Statistical Program, version 6 (Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, USA). The obtained data were tabulated using methods of proportion, χ 2 and paired t-tests. A P value less than 0.05 was accepted as the level of statistical significance.


  Results Top


The present study evaluated 30 patients with active-phase PD and 20 healthy volunteers who served as the control group.

The patients’ ages ranged from 26 to 63 years with a mean of 44.4±10.4 years, whereas the ages of the control individuals ranged from 22 to 59 years with a mean of 42.7±11.3 years. There was a statistically insignificant difference between the two groups. As regards special habits, 50% of patients were smokers, compared with 40% of the control group, with no statistically significant difference between the two groups [Table 1].
Table 1: General characteristics of the studied groups

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As regards marital status 96.7% of the patients were married, compared with 60% of the control group, with significant statistical difference between the two groups [Table 1].

In the current study, the most common manifesting complaint was a palpable and painful penile plaque, which was seen in 53.4% of patients (n=16).

As regards the history of systemic illness, 13.3% (n=4) of patients had a positive history of diabetes mellitus and 16.7% (n=5) had a history of hypertension, whereas none of the individuals in the control group had a history for either illness.

Plasma TGF-β1 levels ranged from 2700 to 30 000 among patients, with a mean of 16410±10610.2, whereas in the control group it ranged from 1200 to 2300 with a mean of 1769.5±334.8. There was a statistically significant difference as regards plasma TGF-β1 between the two groups (P<0.05; [Table 2].
Table 2: Comparison of plasma-transforming growth factor-β1 between patients and controls

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There was a statistically significant difference between patients and controls as regards the relationship between TGF-β 1 plasma levels and patients’ complaints [Table 3].
Table 3: Comparison of plasma-transforming growth factor-β1 levels of patients according to patients’ complaints

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In the present study there was a significant difference between TGF-β1 levels in patients with diabetes or hypertension when compared with controls [Table 4].
Table 4: Comparison of plasma-transforming growth factor-β1 levels in patients with diabetes mellitus and hypertension

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Using linear regression analysis, a significant correlation was seen between age and TGF-β1 levels in patients, but no correlation was observed in the control group [Table 5] and [Figure 1].
Table 5: Correlation between TGF-β1 and age in the studied groups by linear regression analysis

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Figure 1: Linear regression analysis of transforming growth factor-β1 (TGF-β1) in the patient group shows significant correlation with age.

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  Discussion Top


Attention has been focused on the role of TGF-β1 as a fibrogenic cytokine that induces fibrosis in a variety of organs including the penis 6.

In the current study, we measured plasma TGF-β1 levels from peripheral blood samples obtained from 30 patients classified as having acute-phase PD and from 20 healthy volunteers who served as controls.

A significant increase in plasma TGF-β1 levels in the PD patient group was found in comparison with controls (P=0.05). These results augment the role of TGF-β1 in the pathogenesis of PD and are in agreement with the results of Zimmermann et al. 7 who also found a significant increase in TGF-β1 levels in PD patients in comparison with controls. In the study by Zimmermann et al. 7 patients at both stages of the disease were enrolled: those in active-phase PD, as denoted by the presence of a painful plaque, and those with stable-stage PD, which was determined on the basis of a 12-month duration of illness together with manifested erectile dysfunction, which is a sequel of stable PD. To our knowledge, apart from the study by Zimmermann et al. 7 and the current study no other studies have assessed TGF-β1 levels in PD patients using blood samples.

As regards the association between plasma TGF-β1 levels and the presence of risk factors such as diabetes mellitus and hypertension, our study has shown a statistically significantly higher level of plasma TGF-β1in diabetic and hypertensive PD patients than in PD patients without these risk factors. However, these results are limited by the small number of diabetic and hypertensive patients in this study.

Goldfarb and Ziyadeh 9 reported elevation of TGF-β1 levels in patients suffering from diabetes with no other pathology, but they attributed this elevation to the presence of associated diabetic neuropathy.

A report addressed the elevation of TGF-β1 in patients with hypertension, which was attributed to the presence of renal affection and ventricular hypertrophy 10.

On performing linear regression analysis, significant correlation was observed between TGF-β1 levels and age in the studied group but not among controls. This suggest that TGF-β1 is sensitive to age, which was addressed by Okamoto et al. 11, who found age-related differences in TGF-β1 levels in two different age groups.

Also the negative correlation of age in the control group may be attributed to the possibility that patients who have PD have an underlying vascular insult related to age, which aids in the pathogenesis of PD and subsequent elevation of TGF-β1 levels not present in controls.

A larger-scale study is needed to address the role and sensitivity of plasma TGF-β1 levels as a diagnostic and therapeutic marker for PD, as assessment of plasma TGF-β1 in peripheral blood is a simple and effective method for detecting cavernous TGF-β1 expression without the need for penile biopsies or studying penile samples. TGF-β1 may by a target for developing new therapeutics that block TGF-β1 signaling and hence improve PD. It can also act as a marker for PD therapy and aid in evaluation of the disease phase.[11]

 
  References Top

1.Mulhall JP, Schiff J, Guhring P.An analysis of the natural history of Peyronie’s disease.J Urol 2006;175:2115–2118.  Back to cited text no. 1
    
2. Jalkut M, Gonzalez-Cadavid N, Rajfer J.Peyronie’s disease: a review.Rev Urol 2003;5:142–148.  Back to cited text no. 2
    
3. Kumar R.Surgical and minimally invasive treatments for Peyronie’s disease.Curr Opin Urol 2009;19:589–603.  Back to cited text no. 3
    
4. Leffell MS.Is there an immunogenetic basis for Peyronie’s disease.J Urol 1997;157:295–297.  Back to cited text no. 4
    
5. Blobe GC, Schiemann WP, Lodish HF.Role of transforming growth factor β in human disease.N Engl J Med 2000;342:1350–1358.  Back to cited text no. 5
    
6. Ryu JK, Song SU, Chio HK, Seong DH, Yoon SM, Kim SJ, Suh JK.Plasma transforming growth factor- β 1 levels in patients with erectile dysfunction.Asian J Androl 2004;6:349–353.  Back to cited text no. 6
    
7. Zimmermann R, Gerhard F, Conny B, Lorenz H, Arnulf S.Significant alterations of serum cytokine levels in patients with Peyronie’s disease.Int Braz J Urol 2008;34:457–466.  Back to cited text no. 7
    
8. Palmieri A, Imbimbo C, Longo N, Fusco F, Verze P, Mangiapia F, et al..A first prospective, randomized, double-blind, placebo-controlled clinical trial evaluating extracorporeal shock wave therapy for the treatment of Peyronie’s disease.Eur Urol 2009;56:363–369.  Back to cited text no. 8
    
9. Goldfarb S, Ziyadeh F.TGF-beta: a crucial component of the pathogenesis of diabetic nephropathy.Trans Am Clin Climatol Assoc 2001;112:27–33.  Back to cited text no. 9
    
10. Lijnen PJ, Petrov VV, Fagard RH.Association between transforming growth factor-beta and hypertension.Am J Hypertens 2003;16:604–611.  Back to cited text no. 10
    
11. Okamoto Y, Gotoh Y, Uemura O, Tanaka S, Ando T, Nishida M.Age-dependent decrease in serum transforming growth factor (TGF)-beta 1 in healthy Japanese individuals; population study of serum TGF-beta 1 level in Japanese.Dis Markers 2005;21:71–74.  Back to cited text no. 11
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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  In this article
Abstract
Introduction
Patients and methods
Results
Discussion
Introduction
Patients and methods
Results
Discussion
References
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