Regulation of the induction of a cytochrome P-450 prostaglandin omega-hydroxylase by pregnancy in rabbit lung

The mechanism of induction of an adult rabbit cytochrome P-450, prostaglandin (PG) ω -hydroxylase (P-450PG-ω), during pregnancy has been investigated. This P-450 isozyme regiospecifically hydroxylates PGE1, PGA1, and PGF2α at carbon-20 (the ω position). The specific activity of this enzyme is induced from 0.07 nmol of 20-OH-PGE1 to 3.05 nmol of 20-OH-PGE1 formed per min per mg of microsomal protein in the lungs of 25- to 28-day pregnant rabbits as compared to nonpregnant rabbits. Immunoblotting studies with a polyclonal antibody raised against this P-450 have shown that there is a concomitant gestational age-dependent increase in the amount of P-450PG-ω microsomal protein accompanying the increase of ω -hydroxylase activities. Within 3 days postpartum, both ω -hydroxylase activity and the amount of immunodetectable P-450PG-ω drop precipitously to near control levels. In vitro translation of total cellular RNA, extracted from the lungs of pregnant rabbits at various days throughout gestation, and immunoprecipitation of newly synthesized P-450PG-ω demonstrated a similar gestational age-dependent increase in translatable P-450PG-ω mRNA, as was observed with ω -hydroxylase activity and P-450PG-ω protein levels. These data suggest that the induction of this P-450 may occur at the transcriptional level and, furthermore, that control of cytochrome P-450PG-ω expression in the rabbit lung is tightly regulated at both protein and mRNA levels.