RAPID AND SLOW HYDROXYLATORS OF SEMINAL E-PROSTAGLANDINS AMONG MEN INBARREN UNIONS

E prostaglandins are formed in seminal vesicles and can be oxygenated by (pi-1)-hydroxylation catalysed by cytochrome P450 to 19(R)-hydroxy metabolites. The latter are not further metabolized. Prostaglandin E(1 ) (PGE(1)), PGE(2), 19-hydroxy-PGE(1) and 19-hydroxy-PGE(2) were measu red in seminal fluid of 95 men, who attended the clinic for infertilit y. After extractive isolation, the E prostaglandins were converted to B prostaglandins by alkali treatment and analysed by high performance liquid chromatography on beta-cyclodextrin silica with 17-phenyl-PGE(2 ), as an internal standard. The relative amount of 19-hydroxy E-prosta glandins varied between 26% and 97%. Most (86%) of the men were classi fied as rapid or normal hydroxylators with PGE/19-hydroxy PGE ratios b elow 0.75, while 14% were slow hydroxylators. The relative amount of 1 9-hydroxy E(1) and 19-hydroxy E(2) showed a 96% covariation, which sup ports that a common enzymatic mechanism is operating on both E(1) and E(2) prostaglandins and that this mechanism is the major determinant f or formation of 19-hydroxy compounds. We conclude that the relative am ounts of PGE(1), PGE(2), 19-hydroxy-PGE(1) and 19-hydroxy-PGE(2) in se minal fluid vary, possibly due to polymorphic expression of this enzym atic mechanism. Total output of 19-hydroxy-PGE compounds, but not the primary PGE compounds was correlated with the output of seminal fructo se, supporting that the 19-hydroxy prostaglandins are the normal end p roducts of the seminal vesicles. Low sperm concentration found among m en with high output of E prostaglandins could here simply be explained by dilution of spermatozoa by a high output of seminal vesicular flui d. Rapid and slow hydroxylators revealed no difference in time of abst inence or in total output of E prostaglandins, sperm number, semen vol ume or total output of fluid from the seminal vesicles and prostate. T he physiological significance of the variation in seminal E prostaglan dins and 19-hydroxylation, respectively, remains unclear.