INVESTIGATIVE UROLOGY

Immunohistochemical Distribution of cAMP- and cGMP-Phosphodiesterase (PDE) Isoenzymes in the Human Prostate
Uckert S, Oelke M, Stief CG, Andersson KE, Jonas U, Hedlund P
Hannover Medical School, Department of Urology, Hannover, Germany
Eur Urol. 2006; 49: 740-5

• Objectives: With the introduction of sildenafil citrate (VIAGRA trade mark), the concept of phosphodiesterase (PDE) inhibition has gained tremendous interest in the field of urology. Cyclic nucleotide second messengers cGMP and cAMP have been assumed to be involved in the control of the normal function of the prostate. The aim of the present study was to evaluate by means of immunohistochemistry the expression and distribution of some cAMP- and cGMP-PDE isoenzymes in the prostate.
• Material & Methods: Cryostat sections (10muM) of formaldehyde-fixated tissue segments excised from the transition zone of human prostates were incubated with primary antibodies directed against the PDE isoenzymes 3, 4, 5, and 11. Then, sections were exposed to either fluorescein isothiocyanate- (FITC) or Texas Red- (TR) labeled secondary antibodies and visualization was commenced by means of laser fluorescence microscopy.
• Results: TR-immunofluorescence indicating the presence of PDE4 (cAMP-PDE) was abundantly observed in the fibromuscular stroma as well as in glandular structures of the transition zone. In contrast to the distribution of PDE4, immunoactivity indicating PDE5 (cGMP-PDE) and 11 (dual substrate PDE) was mainly observed in glandular and subglandular areas. No immunostaining for PDE3 (cGMP-inhibited PDE) was detected.
• Conclusion: Our results confirm the presence of PDE isoenzymes 4, 5 and 11 in the transition zone of the human prostate and present evidence that these isoenzymes are not evenly distributed. These findings are in support of the hypothesis that there might be a rationale for the use of PDE inhibitors in the pharmacotherapy of BPH and LUTS.
  
  
• Editorial Comment
  Lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) association is a very much discussed theme in urology practice and many papers have been published during the last few years. Prostatic obstruction may be clinically treated either by alpha-blockers (effect on bladder neck) or by 5-alpha-reductase inhibitors (reducing effect on gland volume) (1). Recent research (2,3) suggests that the combination of an alpha-blocker and a phosphodiesterase type 5 inhibitor may be useful in patients with (LUTS) associated with erectile dysfunction. The present paper demonstrates the pharmacological background for previous clinical findings.

References
1. Desgrandchamps F: Combination therapy in benign prostatic hyperplasia (BPH). Ann Urol (Paris). 2004; 38 Suppl 2: S24-8.
2. Carson CC: Combination of phosphodiesterase-5 inhibitors and alpha-blockers in patients with benign prostatic hyperplasia: treatments of lower urinary tract symptoms, erectile dysfunction, or both? BJU Int. 2006; 97 Suppl 2: 39-43; discussion 44-5.
3. Yassin A, Saad F, Hoesl CE, Traish AM, Hammadeh M, Shabsigh R: Alpha-adrenoceptors are a common denominator in the pathophysiology of erectile function and BPH/LUTS—implications for clinical practice. Andrologia. 2006; 38: 1-12.

Dr. Francisco Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil