The role of prostaglandins in masculine differentiation: modulation of prostaglandin levels in the differentiating genital tract of the fetal mouse.

The present study was designed to test the hypothesis that the stimulation of arachidonic acid prostaglandins (PG) mediates the masculinizing effects of testosterone in the fetal mouse. We examined a number of situations in which masculine organization was either induced or inhibited by external agents and determined whether PG levels in the fetal genital tracts were altered in a manner coincident with those situations. We show here that both PGE2 and 6-keto-PGF1 alpha levels in the male fetal genital tracts increased with the advancement of masculine differentiation. PG levels in males (1.2 +/- 0.3 pg PGE2 and 0.1 +/- 0.03 pg 6-keto-PGF1 alpha on day 14 of gestation) increased to 2.1 +/- 0.3 pg PGE2 and 1.2 +/- 0.3 PG 6-keto-PGF1 alpha on day 18 of gestation. The PG levels in the male genital tract were significantly higher than the PG levels in the female genital tract throughout the period of sexual differentiation. Before this period, however, such as on day 14 of gestation (when male and female fetuses have identical genital tracts) we found no difference in their PG levels. Moreover, administration of testosterone (40 mg/kg) during the critical period of masculine differentiation (days 13-17 of gestation) significantly increased PG levels (approximately 2-fold) of female fetuses. Furthermore, we found that cyproterone acetate (20 mg/kg), an inhibitor of masculine differentiation, on days 13-17 of gestation deceased PG levels in male fetuses. In addition, administration of PG synthesis inhibitors, namely indomethacin (1 mg/kg) and aspirin (100 mg/kg), inhibited both resting and androgen-inducible PG levels in male and female fetuses. Considering these results together, it may be concluded that PGs have a critical role in the masculinizing action of fetal testosterone.