Role of the free radical-scavenger system in aromatase activity of the human ovary.
The present study was undertaken to clarify the physiological role of the free radical-scavenger system in the control of estrogen production in the human ovary with age. Both superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the homogenate of the ovary significantly decreased from the premenopausal period to the menopausal period. The lipid peroxide content, however, showed a small and gradual decrease from the premenopausal to the postmenopausal period. In the premenopausal women, aromatase (Ar) activity in the microsomal fraction of the ovary showed a sharp decline and a significant negative correlation with age. Significant positive correlations were found between SOD and Ar activity, and between GSH-Px and Ar activity. Treatments of homogenate of the ovary with 10, 50 and 100 microM of H2O2 resulted in a decrease in Ar activity in a dose-dependent manner. Moreover, treatment with 10 and 50 microM of H2O2 produced a more significant decrease in the Ar activity in the premenopausal women than that in the postmenopausal women. Treatments with 0.01, 0.1, 1.0 and 10.0 U of GSH-Px before administration of 50 microM of H2O2, on the other hand, induced a recovery of the Ar activity in a dose-dependent manner. The present study showed the inhibitory effect of peroxide on Ar activity, which was attenuated by GSH-Px. These results seem to suggest that these age-related, relatively free radical predominant environments in the human ovary may have an important role in the decrease of estrogen production through the effects on the Ar activity.
Okatani
Y
Y
Department of Obstetrics and Gynecology, Kochi Medical School, Japan.
Morioka
N
N
Wakatsuki
A
A
Nakano
Y
Y
Sagara
Y
Y
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors; D004305:Dose-Response Relationship, Drug; D005260:Female; D016166:Free Radical Scavengers; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008054:Lipid Peroxides / Q000032:analysis / Q000378:metabolism; D008593:Menopause / Q000378:metabolism; D008861:Microsomes / Q000201:enzymology; D008875:Middle Aged; D010053:Ovary / Q000737:chemistry / Q000201:enzymology* / Q000648:ultrastructure; D013482:Superoxide Dismutase / Q000378:metabolism
D047072:Aromatase Inhibitors; D016166:Free Radical Scavengers; D008054:Lipid Peroxides; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D001141:Aromatase; D013482:Superoxide Dismutase