Prostanoids produce significant effects in the ureter, particularly in response to obstruction.
Ureteral obstruction is associated with increased
prostanoid synthesis via
cyclooxygenase induction; however,
prostaglandin degradation mediated by
15-hydroxyprostaglandin dehydrogenase (PGDH) has not been evaluated in the ureter. The purpose of this study was to determine whether PGDH steady-state
mRNA,
protein, and
enzyme activity are altered in the human ureter during obstruction. Human ureteral segments from patients undergoing donor
nephrectomy (normal segments) or ureteral
stricture repair (obstructed segments) were obtained with proper informed consent. We evaluated PGDH steady-state
mRNA relative to
ribosomal protein S26 reference gene by reverse transcription-polymerase chain reaction and Vistra Green fluoroimaging. We determined PGDH
protein content relative to
glyceraldehyde-3-phosphate dehydrogenase by immunoblotting and PGDH localization by immunohistochemistry. PGDH enzymatic activity was determined by measurement of conversion of 15-hydroxy- to 15-keto-prostaglandin using thin layer chromatography separation. We found that PGDH
mRNA and
protein were decreased 4- to 6-fold, and
enzyme activity was decreased >3-fold in obstructed human ureter relative to normal controls. PGDH was localized to the urothelial cells, with little or no expression in smooth muscle. Our results indicate that PGDH
mRNA,
protein, and
enzyme activity are suppressed in the human ureter during obstruction. Increased concentrations of
prostanoids subsequent to
ureteral obstruction seem to be due to decreased degradation as well as increased synthesis. Modulation of
prostanoid degradation may have therapeutic relevance in obstructive disorders of the ureter.