In vitro 19-norandrogen synthesis by equine placenta requires the participation of aromatase.
Explants of equine full-term placenta have been shown to synthesize 19-norandrogens from labelled androgens. Steroid metabolites were purified by silica-gel column chromatography then analysed and quantified by c18-reverse-phase HPLC coupled to a radioactive flow detector. 19-Norandrostenedione was subsequently recrystallized to constant specific activity, providing unequivocal evidence of its synthesis by the equine placenta. 19-Norandrostenedione synthesis appeared to be localized in the microsomal fraction. Regardless of the substrate used, formation of 19-norandrogens was far weaker than that of oestrogens; moreover, the yield of 17-oxosteroids produced was much greater than that of 17 beta-hydroxysteroids, suggesting the presence of a dehydrogenase with predominant oxidative activity. Sulphoconjugated steroids formed were less than 0.5% of total steroids. Although 19-nortestosterone could not be generated by equine purified aromatase incubated with labelled testosterone, the synthesis of 19-norandrogens and oestrogens by equine placental explants was blocked by two specific aromatase inhibitors, 4-hydroxyandrostenedione and fadrozole. Our results provide evidence for a placental origin of at least a part of the 19-norandrogens previously identified in the blood of the pregnant mare. Furthermore, it is suggested that 19-norandrogen biosynthesis would involve the enzymatic metabolism of 19-oxygenated androgens formed by equine aromatase.
Moslemi
S
S
Laboratoire de Biochimie, Centre National de la Recherche Scientifique URA 609, Université de Caen, France.
Silberzahn
P
P
Gaillard
J L
JL
D000735:Androstenedione / Q000031:analogs & derivatives* / Q000096:biosynthesis; D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006736:Horses / Q000378:metabolism*; D009924:Organ Culture Techniques; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
D000735:Androstenedione; D001141:Aromatase; C002828:19-norandrostenedione