Document Detail

Developmental regulation of flavin-containing monooxygenase (FMO) isoforms 1 and 2 in pregnant rabbit.
MedLine Citation:
PMID:  7720106     Owner:  NLM     Status:  MEDLINE    
Mammalian flavin-containing monooxygenase (FMO, EC metabolizes a vast number of structurally diverse xenobiotics containing a soft-nucleophile, typically a nitrogen or sulfur. FMO is not inducible by the classical cytochrome P450 (CYP) inducers, such as phenobarbital, polycyclic aromatic hydrocarbons, ethanol or macrolide antibiotics. Evidence does exist from a number of laboratories, however, for developmental and hormonal regulation of FMO. Our laboratory has confirmed previous observations of enhanced FMO activity during mid- and late-gestation in maternal rabbit lung and have demonstrated that this response is due to increased protein and catalytic activity associated with FMO2. The time course of expression of FMO2 during mid- and late-gestation correlates to plasma peaks of progesterone or cortisol. FMO2 also peaks at parturition in maternal kidney, coincident with plasma cortisol levels. FMO2 is induced by s.c. administration of either progesterone or dexamethasone in lung, or by dexamethasone in kidney. Correlation of plasma progesterone or cortisol levels during gestation and postpartum support a role for progesterone, but not cortisol in regulation of FMO2 in maternal rabbit lung. The levels of FMO1 also appear to be increased during mid- and late-gestation in liver. FMO1 in liver may also be regulated during gestation by progesterone or glucocorticoids as administration of these steroids enhanced FMO1 mRNA levels 4-fold.
M Y Lee; S Smiley; S Kadkhodayan; R N Hines; D E Williams
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Chemico-biological interactions     Volume:  96     ISSN:  0009-2797     ISO Abbreviation:  Chem. Biol. Interact.     Publication Date:  1995 Apr 
Date Detail:
Created Date:  1995-05-25     Completed Date:  1995-05-25     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0227276     Medline TA:  Chem Biol Interact     Country:  IRELAND    
Other Details:
Languages:  eng     Pagination:  75-85     Citation Subset:  IM    
Toxicology Program, Oregon State University, Corvallis, USA.
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MeSH Terms
Blotting, Western
Dexamethasone / administration & dosage,  pharmacology
Enzyme Induction / drug effects
Flavins / metabolism*
Gene Expression Regulation, Developmental / genetics
Kidney / drug effects,  enzymology
Lung / drug effects,  enzymology
Oxygenases / genetics*,  metabolism
Postpartum Period / metabolism
Pregnancy, Animal / metabolism*
Progesterone / administration & dosage,  pharmacology
RNA, Messenger / genetics,  metabolism
Urinary Bladder / enzymology
Xenobiotics / metabolism
Grant Support
Reg. No./Substance:
0/Flavins; 0/RNA, Messenger; 0/Xenobiotics; 50-02-2/Dexamethasone; 57-83-0/Progesterone; EC 1.13.-/Oxygenases; EC monooxygenase (N-oxide forming)

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