Different in vitro metabolism of 7 alpha-methyl-19-nortestosterone by human and equine aromatases.
The ability of human and equine placental microsomes to aromatize 7 alpha-methyl-19-nortestosterone (MNT) was studied. Kinetic analysis indicates that MNT shares the androgen-binding site of human and equine placental microsomal aromatases. Human placental microsomal estrogen synthetase had about a 2.5-fold higher relative affinity for MNT than the equine placental enzyme (KiMNT/Km androstenedione of 32 versus 87). However, MNT was not metabolized by human placental microsomes, whereas it was very actively metabolized by equine placental microsomes. Further studies using purified equine cytochrome P-450arom indicated that the presence of a 7 alpha-methyl group and the absence of a C19 methyl group did not impair its conversion by the purified enzyme. The product of this reaction was separated and identified as 7 alpha-methylestradiol by gas chromatography coupled to mass spectrometry.
Laboratoire de Biochimie, Centre National de la Recherche Scientifique URA 609, Université de Caen, France.
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Moslemi
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Dintinger
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Dehennin
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P
Silberzahn
J L
JL
Gaillard
D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors; D001665:Binding Sites; D004963:Estrenes / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006736:Horses; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology; D009277:Nandrolone / Q000031:analogs & derivatives*; D010920:Placenta / Q000201:enzymology* / Q000648:ultrastructure; D011247:Pregnancy
D047072:Aromatase Inhibitors; D004963:Estrenes; C064709:trestolone; D009277:Nandrolone; D001141:Aromatase