Effects of obesity on estradiol metabolism: decreased formation of nonuterotropic metabolites.
Obesity is associated with an increased incidence of reproductive dysfunction and estrogen-linked diseases. In the present study, we have examined the principal oxidative biotransformations of estradiol in 13 obese premenopausal females and 10 obese males compared to those in 9 premenopausal female and 15 male controls. These studies were carried out using a recently devised, sensitive radiometric method which permits the assessment of the total in vivo oxidative metabolism of estradiol at specific sites (i.e. 17 alpha, 16 alpha, or C-2) on the steroid molecule. Our results indicate that obesity (greater than 60% above ideal body weight) is associated with significant decreases in hydroxylation at C-2 in both sexes (P less than 0.001 for females and P less than 0.02 for males) and in oxidation at 17 alpha in premenopausal females (P less than 0.05) compared to that in age-matched, normal weight controls. Analysis of the plasma 3H2O specific activity curves suggested a slight decrease in the rate of 17-oxidation in obese subjects. The extent of hydroxylation at 16 alpha was not significantly affected by obesity. These metabolic alterations documented in obesity could result in a relative hyperestrogenic state, since, unlike the other estrogen metabolites, the 2-hydroxyestrogen compounds display relatively little peripheral estrogenic activity. This metabolic alteration on a prolonged basis might be contributory to the prevalence of certain hormonally related diseases in obese individuals.
D000328:Adult; D055598:Chemical Phenomena; D002621:Chemistry; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism*; D005260:Female; D006801:Humans; D006900:Hydroxylation; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D010084:Oxidation-Reduction; D012737:Sex Factors; D014316:Tritium
D014316:Tritium; D004958:Estradiol; C001390:2-hydroxyestradiol