Evidence for interference in estradiol-17beta inactivation to estrone by oxidized low-density lipoprotein and selected lipid peroxidation products.
An elevation in plasma estrogen levels is believed to play a key role in the pathogenesis of breast cancer. The conversion of estradiol-17beta (E2) to estrone (E1) by 17beta-hydroxy steroid dehydrogenase type 4 (17-HSD4) represents a major pathway of its inactivation in cells. In this study the potential relationship between lipoprotein peroxidation products and E2 metabolism was examined. It was noted that oxidized low-density lipoprotein (OX-LDL), not native LDL, caused a time- and concentration-dependent inhibition of the conversion of labeled E2 to E1 in THP-1 macrophage cells. Further studies noted that among the lipoprotein peroxidation products examined, malondialdehyde (MDA) caused a marked decrease in this reaction, whereas hexanal and a variety of oxysterols had no effect. This inhibition of E1 formation from E2 in THP-1 cells was confirmed by the quantitation of estrone formed with high-pressure liquid chromatography and by the expression of 17-HSD4 by reverse transcriptase-polymerase chain reaction. MDA added to Hep G2 cells showed a similar trend in E1 formation. These results suggest that increased oxidative stress and lipid peroxidation might result in decreased inactivation of biologically active estrogen. This might be important in postmenopausal women undergoing estrogen replacement therapy.
Abplanalp
W
W
Department of Internal Medicine, University of Cincinnati Medical Center, Ohio 45267, USA.
Rymaszewski
M
M
Adamski
J
J
Subbiah
M T
MT
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001943:Breast Neoplasms / Q000209:etiology / Q000378:metabolism; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004958:Estradiol / Q000378:metabolism*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D004970:Estrone / Q000378:metabolism*; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008593:Menopause / Q000378:metabolism; D010084:Oxidation-Reduction
D017931:DNA Primers; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D004970:Estrone; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases