15- and 16-hydroxylations of androgens and estrogens in the human fetal liver: a critical step in estetrol biosynthesis.
To elucidate the main metabolic pathways which lead to the foeto-placental biosynthesis of estetrol (I), we investigated the 15 alpha- and 16 alpha-hydroxylations of potential precursors of this estrogen in the human fetal liver. We determined the 15 alpha- and 16 alpha-hydroxylation capacity of the fetal liver for each precursor by GC-MS. The results suggest that estetrol is derived only from estradiol sulfate (II) and DHEA sulfate (III). 15 alpha-Hydroxy-androstenedione (IV) can no longer be regarded as a good precursor of estetrol. The phenolic pathway appears to be a more likely route than the neutral pathway, even when derived from DHEA sulfate.
Cantineau
R
R
Kremers
P
P
De Graeve
J
J
Gielen
J E
JE
Lambotte
R
R
D000728:Androgens / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases; D055598:Chemical Phenomena; D002621:Chemistry; D065727:Cytochrome P-450 CYP2C8; D065729:Cytochrome P-450 CYP2C9; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate; D004953:Estetrol / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism; D004964:Estriol / Q000031:analogs & derivatives*; D004967:Estrogens / Q000378:metabolism; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D039181:Steroid 16-alpha-Hydroxylase
D000728:Androgens; D004967:Estrogens; C031555:estradiol sulfate; D003687:Dehydroepiandrosterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; D039181:Steroid 16-alpha-Hydroxylase; D004953:Estetrol; D004964:Estriol