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Altered Growth Factor Expression in the Aging Penis: The Brown-Norway Rat Model

SAE-WOONG KIM

MANOJ MONGA

From the ^* Division of Urology, University of California San Diego Medical Center, San Diego, California; and the Veterans Medical Research Foundation, San Diego, California.

Correspondence to: Dr Mahadevan Rajasekaran, c/o Janell Poehling, Division of Urology, University of California San Diego Medical Center, 200 W Arbor Dr, San Diego, CA 92103-8897 (e-mail: mrajasek{at}ucsd.edu ).

The objective of the present study was to evaluate age-related changes in the protein and gene expression of modulators of erectile function (nitric oxide [NO] and endothelin-1 [ET-1]) and growth factors such as transforming growth factor (TGF-ß1) and vascular endothelial growth factor (VEGF) in the penile tissue of Brown-Norway (BN) rats. Young and old BN male rats were euthanized, and the penile tissue was processed for immunohistochemical and molecular analyses. Total RNA was extracted, and an Access reverse transcription-polymerase chain reaction (RT-PCR) system was used for messenger RNA (mRNA) expression analysis. Immunohistochemical studies showed a decreased expression of endothelial nitric oxide synthase (eNOS) protein and an increased staining for ET-1. Quantitative analysis of PCR products revealed decreased levels of VEGF mRNA expression in the old population of rats. The most significant decrease was detected between bands corresponding to splice forms 164 (21%) and 120 (18%). The observed alterations in the gene expression of growth factors such as VEGF may contribute to the abnormal age-related morphological and physiological alterations in the erectile tissue.

     Key words: Aging, erectile dysfunction, nitric oxide, endothelins, vascular endothelial growth factor, transforming growth factor

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