Investigation of the mechanisms of estradiol insensitivity in the female squirrel monkey
The reproductively active female squirrel monkey is characterized by markedly elevated plasma estradiol levels. Plasma estradiol levels have been reported to be 10 to 30 times that in Old World primates and humans. However, the exact mechanisms responsible for these elevated estradiol concentrations...
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| Format: | Others |
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DigitalCommons@Robert W. Woodruff Library, Atlanta University Center
1993
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| Online Access: | http://digitalcommons.auctr.edu/dissertations/632 http://digitalcommons.auctr.edu/cgi/viewcontent.cgi?article=2179&context=dissertations |
| Summary: | The reproductively active female squirrel monkey is characterized by markedly elevated plasma estradiol levels. Plasma estradiol levels have been reported to be 10 to 30 times that in Old World primates and humans. However, the exact mechanisms responsible for these elevated estradiol concentrations have not been fully elucidated. In this study, two possible mechanisms contributing to elevated steroid levels were investigated. Investigation of uterine estrogen receptor binding parameters using the nuclear exchange method, revealed a uterine receptor concentration of 228 ±17.6 pmol/1 and a dissociation constant of 2.80 ±0.24 nM. Nuclear receptor levels were found to be 46.0 ±19.4 pmol/1 with a dissociation constant of 5.42 ±1.92 nM. Intravenous administration of [3H]-estradiol, followed by subsequent collection of urine and feces at 24 h intervals for a duration of 96 h, revealed that 71.4 % of the administered radiolabeled estradiol was recovered in the feces with only a 4.23 % recovery of radiolabeled estrogen in the urinary pool. Subsequent isolation and identification of estrogen metabolites by standard procedures including ion exchange chromatography and TLC, revealed that sulfate conjugates represented the major metabolites, with E217S accounting for over 55% of the total administered dose. Recovery of glucosiduronate conjugates in both urine and feces was minimal. Subsequent in vitro liver preparation, that involved characterization of E2-17ß sulfo-transferase activity in cytosol fractions, revealed that the female squirrel monkey may possess a sulfotransferase that is specific for estradiol sulfation at the C-17ß position. This enzyme could in effect reduce estrogenicity by masking the C-17 hydroxyl group necessary for activity. |
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