Korean J Urol.  2006 Nov;47(11):1178-1184. 10.4111/kju.2006.47.11.1178.

Effect of 5alpha-Reductase Inhibitor in Expression of Transforming Growth Factor-beta1 in Benign Prostatic Hyperplasia Patients

• Kim HW
• Lim JS
• Chang YS
• Son KH

• KMID: 2294276
• DOI: http://doi.org/10.4111/kju.2006.47.11.1178

Abstract

Purpose
Transforming growth factor (TGF)-beta is a member of the superfamily of polypeptides, which control cell cycle progression and a variety of other cellular activities. TGF-beta1 has been implicated as an effector of the induction of apoptosis in response to 5alpha-reductase inhibitor (5ARI) and; therefore, causes a decrease in the prostate volume. We investigated the effect of 5ARI in the expression of TGF-beta1 in benign prostatic hyperplasia (BPH).
Materials and Methods
50 patients diagnosed with BPH were divided into two groups. The control group (n=30), in which a transurethral resection of the prostate (TURP) was performed without medication, and the 5ARI group (n=20), who were administrated with 5 mg of 5ARI daily for at least 3 months, followed by TURP. The resected specimens were stained with anti-rabbit TGF-beta1 polyclonal antibody using immunofluoroscent staining. The expression of TGF-beta1 was analyzed with a confocal laser scanning microscope and an image analyzer. The mRNA level of TGF-beta1 was determined by reverse transcriptase-polymerase chain reaction (RT-PCR).
Results
There were no statistical differences in the patient characteristics, including age, serum prostate-specific antigen (PSA) level and prostate volume, between the two groups. The expression of TGF-beta1 was demonstrated in the luminal epithelium and smooth muscle cells in BPH. TGF-beta1 was more strongly expressed in the luminal epithelium of both groups, and in the 5ARI group than the control (p<0.001).
Conclusions
These results suggest that 5ARI up-regulates the expression of TGF-beta1 in BPH patients, and may a play role as an inhibitor in the proliferation of BPH through the TGF-beta1 signal pathway.

Keyword

Benign prostatic hyperplasia; 5alpha-reductase; Transforming growth factor-beta1

MeSH Terms

Apoptosis
Cell Cycle
Epithelium
Humans
Myocytes, Smooth Muscle
Peptides
Phenobarbital
Prostate
Prostate-Specific Antigen
Prostatic Hyperplasia*
RNA, Messenger
Signal Transduction
Transforming Growth Factor beta1
Transforming Growth Factors
Transurethral Resection of Prostate
Peptides
Phenobarbital
Prostate-Specific Antigen
RNA, Messenger
Transforming Growth Factor beta1
Transforming Growth Factors

Figure

• 

  Fig. 1 Immunofluoroscent staining of TGF-β1 in the control and 5ARI groups (×400). (A), (D): DAPI staining of the nucleus in BPH specimens. (B), (E): the 5ARI group shows stronger expression of TGF-β1 than the control group. The gland area (arrow) expresses stronger TGF-β1 immunoactivity than the stromal area (arrowhead) in the 5ARI group. (C), (F): merged image of TGF-β1 (A-C: 5ARI group. D-F: control group.). 5ARI: 5alpha-reductase inhibitor, TGF: transforming growth factor, BPH: benign prostatic hyperplasia.

• 

  Fig. 2 The intensity of TGF-β1 in the immunofluoroscent staining. The glandular area expresses stronger TGF-β1 immunoactivity than the stromal area in both the control and 5ARI groups (p<0.05). The expression of TGF-β1 is not significantly stronger in the stroma of the control group (p>0.05). There is a significantly stronger expression of TGF-β1 in the gland of the 5ARI group (p<0.05). The total intensity of TGF-β1 expression in the 5ARI group is stronger than in the control group (p<0.05). *,†: p<0.05. 5ARI: 5alpha-reductase inhibitor, TGF-β1: transforming growth factor-β1.

• 

  Fig. 3 Expression of TGF-β1 mRNA is increased in the 5ARI compared to the control group (M: marker, 1-4: control group, 5-8: 5ARI group). 5ARI: 5alpha-reductase inhibitor, TGF-β1: transforming growth factor-β1.

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