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Introduction and Objectives: Male aging is accompanied by hypogonadism and worsening LUTS/BPH.The hypogondal state should lead to diminution in LUTS/BPH symptoms. To understand these paradoxical clinical effects, we used a castrate rat model examining contractility and mRNA expression of eNOS, nNOS, PDE5, TGFβ1, ROKα, ROKβ, alpha 1a, alpha 1b, alpha 1d, total myosin, non-muscle myosin and the smooth muscle specific transcriptional factor myocardin.
Methods: Male adult Sprague-Dawley rats (275 to 330 g) were divided into sham, surgical castration, surgical castration with testosterone proprionate (T) supplementation . Organ bath contractility studies, competitive and Real-Time RT-PCR, and histological examination were performed.
Results: The castrate model was validated histologically. The prostate and seminal vesicles atrophied. T supplementation reinstated weight. Total myosin immunostaining was essentially unchanged, though the glandular cells changed morphologically. Castration significantly decreased KCl and phenylephrine (PE)- induced prostate strip contraction in a dose-dependent manner. Alpha receptor subtypes 1a and 1b significantly increased by 2-fold. nNOS decreased 5-fold while eNOS increased 2-fold. ROKβ decreased 2-fold while ROKα showed no change. PDE5 was reduced 3.3-fold. TGFβ1 increased 4-fold. Competitive RT-PCR of the control prostate displayed around 50% SMA and 50% SMB, 85% SM1 and 15% SM2, 70%LC17a and 30%LC17b myosin isoforms. After castration, SMB, SM1 and LC17b increased by 20%, 15% and 5%, respectively. Total myosin, non-muscle myosin and myocardin significantly decreased 2-fold, 5-fold and 3-fold, respectively.
Conclusions:Castration increases prostate alpha 1a and 1b mRNA expression, possibly accounting for LUTS symptoms seen in the aging male faced with hypogonadism.
Source of Funding: NIH