Change of 7alpha-hydroxy-dehydroepiandrosterone levels in serum of mice treated by cytochrome P450-modifying agents.
Dehydroepiandrosterone (DHEA) is 7alpha-hydroxylated in liver, brain and other organs of murine and in other species. Several works suggest that the 7alpha-hydroxy-DHEA produced may be one of the native antiglucocorticoids, and compounds modifying its production may prove useful in investigation of 7alpha-hydroxy-DHEA production and effects. After treatment of mice with dexamethasone, phenobarbital, trilostane, melatonin or metyrapone, we have used gas chromatography-mass spectrometry with negative ion detection for measurement of 7alpha-hydroxy-DHEA levels in serum of control and treated animals. The 7alpha-hydroxylating rates of liver and brain microsomes from the same animals were also measured. Results showed that serum levels of 7alpha-hydroxy-DHEA were significantly increased after treatment by all compounds except metyrapone. Significantly increased 7alpha-hydroxy-DHEA levels were directly related with significantly increased 7alpha-hydroxylation yields in liver and not in brain. In contrast, metyrapone decreased 7alpha-hydroxylation in liver and brain. These findings indicate that in brain and in liver, different enzyme systems may be responsible for production of 7alpha-hydroxy-DHEA and that treatment-induced modifications of circulating 7alpha-hydroxy-DHEA levels are mainly due to change of 7alpha-hydroxylating rates in liver.
Attal-Khémis
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S
Laboratoire de Biotechnologie, Conservatoire National des Arts et Métiers, Paris, France.
Dalmeyda
V
V
Morfin
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R
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D008797:Metyrapone / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology
D013196:Dihydrotestosterone; D003687:Dehydroepiandrosterone; C003587:7-hydroxydehydroepiandrosterone; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D008550:Melatonin; C009954:trilostane; D010634:Phenobarbital; D008797:Metyrapone