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Medientyp:
E-Artikel
Titel:
Regulation of the Induction of a Cytochrome P-450 Prostaglandin ω -hydroxylase by Pregnancy in Rabbit Lung
Beteiligte:
Muerhoff, A. Scott;
Williams, David E.;
Leithauser, Marie T.;
Jackson, Vaughn E.;
Waterman, Michael R.
Erschienen:
National Academy of Sciences of the United States of America, 1987
Erschienen in:
Proceedings of the National Academy of Sciences of the United States of America, 84 (1987) 22, Seite 7911-7914
Sprache:
Englisch
ISSN:
0027-8424
Entstehung:
Anmerkungen:
Beschreibung:
The mechanism of induction of an adult rabbit cytochrome P-450, prostaglandin (PG) ω -hydroxylase (P-450<sub>PG-ω</sub>), during pregnancy has been investigated. This P-450 isozyme regiospecifically hydroxylates PGE<sub>1</sub>, PGA<sub>1</sub>, and PGF<sub>2α</sub> at carbon-20 (the ω position). The specific activity of this enzyme is induced from 0.07 nmol of 20-OH-PGE<sub>1</sub> to 3.05 nmol of 20-OH-PGE<sub>1</sub> 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-450<sub>PG-ω</sub> microsomal protein accompanying the increase of ω -hydroxylase activities. Within 3 days postpartum, both ω -hydroxylase activity and the amount of immunodetectable P-450<sub>PG-ω</sub> 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-450<sub>PG-ω</sub> demonstrated a similar gestational age-dependent increase in translatable P-450<sub>PG-ω</sub> mRNA, as was observed with ω -hydroxylase activity and P-450<sub>PG-ω</sub> 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-450<sub>PG-ω</sub> expression in the rabbit lung is tightly regulated at both protein and mRNA levels.