Rapid and slow hydroxylators of seminal E prostaglandins

Human seminal fluid contains prostaglandin (PG) E1, PGE2, 19-hydroxy-PGE1 and 19-hydroxy-PGE2 in large and variable amounts. 19-Hydroxy-PGE1 and 19-hydroxy-PGE2 are formed from PGE1 and PGE2 by prostaglandin 19-hydroxylase, a cytochrome P-450 enzyme, in seminal vesicles. The hypothesis that genetic polymorphism of this enzyme might contribute to the variable concentrations of PGE1, PGE2, 19-hydroxy-PGE1 and 19-hydroxy-PGE2 was examined by analysis of seminal fluid of 40 normal men. E prostaglandins were measured with 17-phenyl-PGE2 as an internal standard by high-performance liquid chromatography on beta-cyclodextrin silica. Using the ratios of substrate/product, i.e., R1 = PGE1/19-hydroxy-PGE1 and R2 = PGE2/19-hydroxy-PGE2, as indicators of prostaglandin 19-hydroxylase capacity, a bimodal distribution of R values was found: nine men (23%) were slow hydroxylators (R1 greater than 0.45 and R2 greater than 0.45), while the remaining men were rapid hydroxylators (both R1 and R2 less than 0.45). Semen of slow hydroxylators and semen of the five most rapid hydroxylators (both R1 and R2 less than 0.10) differed in absolute amounts of PGE1 and PGE2 but not in 19-hydroxy-PGE1 and 19-hydroxy-PGE2. 20-Hydroxy-PGE1 and 20-hydroxy-PGE2 are formed from PGE1 and PGE2 by cytochrome P-450 in the vesicular glands and the ampullae of deferent ducts of the ram. Seminal fluid of five rams was analyzed for PGE1, PGE2, 20-hydroxy-PGE1 and 20-hydroxy-PGE2, and a large variation in substrate/product ratios was found. Polymorphism of cytochrome P-450 might contribute to variations in seminal prostaglandins in man and in sheep.