ABSTRACT
Vcsa1 plays an important role in the erectile physiology of the rat. We conducted experiments to determine if erectile function, testosterone levels and Vcsa1 expression were correlated. In orchiectomized rats, total testosterone in blood fell from an average of 4 ng/ml to <0.04 ng/ml. Erectile function was significantly lower compared to controls and Vcsa1 expression was significantly (>6-fold) decreased. Injection of orchiectomized animals with testosterone (2 mg in 100ml sesame oil every 4 days for 2 weeks) restored average levels of testosterone to 2 ng/ml, increased erectile function and significantly increased Vcsa1 expression. In isolated corporal cells there was testosterone dependent Vcsa1 expression. However, intracorporal injection of orchiectomized animals with a plasmid expressing Vcsa1 or its gene product Sialorphin (previously demonstrated to improve erectile function in old animals) gave no significant improvement in erectile function. Also, the ability of Sialorphin to reduce tension in corporal smooth muscle strips isolated from orchiectomized animals was impaired compared to controls.
Subject(s)
Gene Expression Regulation/physiology , Penile Erection , Penis/cytology , Protein Precursors/genetics , Salivary Proteins and Peptides/genetics , Testosterone/physiology , Animals , Male , Muscle Contraction , Muscle, Smooth , Orchiectomy , Penis/metabolism , Penis/physiology , Rats , Testosterone/bloodABSTRACT
OBJECTIVE: We investigated the existence and regional distribution of sphingosine-1-phosphate regulatory enzymes and receptors in the lower urinary tract and determined the functional role of sphingosine-1-phosphate receptors in the bladder. STUDY DESIGN: Lower urinary tract tissue from 10 female rats was harvested for real-time reverse transcriptase-polymerase chain reaction or organ bath physiology, whereas blood serum was obtained for high-performance liquid chromatography determination of sphingosine-1-phosphate levels. Statistical analysis included the Student t test and analysis of variance. RESULTS: All 3 sphingosine-1-phosphate receptors and major enzymes were expressed throughout the lower urinary tract, but expression and physiologic force generation varied among regions. Sphingosine-1-phosphate was detected in serum. CONCLUSION: We provide novel data that the sphingosine-1-phosphate signaling pathway regulatory proteins exist throughout the female rat lower urinary tract, but that relative expression exhibits regional heterogeneity corresponding with lower urinary tract contractile response to sphingosine-1-phosphate. Our study suggests that sphingosine-1-phosphate signaling is important in the lower urinary tract and identifies this pathway as a possible target for altering bladder smooth muscle tone.
