title: Metabolism of exogenous 4- and 2-hydroxyestradiol in the human male.
abstract: The metabolic fate of the isomeric catecholestrogens 4-hydroxyestradiol (4-OHE2) and 2-hydroxyestradiol (2-OHE2) was studied to elucidate possible differences in their metabolism as an explanation for their different bioactivities. Healthy young men (n = 3 each) were infused (90 min) with 4-OHE2 (60 micrograms/h) or 2-OHE2 (100 micrograms/h). The main metabolites were determined in plasma and urine before, during and after infusion. Unconjugated and conjugated steroids, the latter after hot acid hydrolysis, were subjected to chromatography on LH-20 columns and measured by specific RIAs. During the infusion 4-OHE2 reached significant plasma concentrations whereas 2-OHE2 was so rapidly metabolised that its plasma levels remained virtually undetectable in spite of a higher infusion rate. The metabolism of 4-OHE2 was dominated by direct conjugation, that of 2-OHE2 by methyl ether formation. These findings were corroborated by the urinary excretion rates: during the infusion and the first hours afterwards, 4-OHE2 was mainly excreted as 4-OHE2 and 4-hydroxyestrone, while 2-OHE2 was predominantly excreted as 2-hydroxyestradiol 2-methyl ether and 2-hydroxyestrone 2-methyl ether.
authors.affiliation: Institut für Biochemische Endokrinologie, Medizinische Universität zu Lübeck, F.R.G.
authors.forename: G
authors.initials: G
authors.lastname: Emons
authors.forename: G R
authors.initials: GR
authors.lastname: Merriam
authors.forename: D
authors.initials: D
authors.lastname: Pfeiffer
authors.forename: D L
authors.initials: DL
authors.lastname: Loriaux
authors.forename: P
authors.initials: P
authors.lastname: Ball
authors.forename: R
authors.initials: R
authors.lastname: Knuppen
mesh_terms: D000328:Adult; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D002393:Estrogens, Catechol / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D013329:Structure-Activity Relationship
chemical_list: D002393:Estrogens, Catechol; D004958:Estradiol; C001390:2-hydroxyestradiol; C014036:4-hydroxyestradiol