Investigation of the mechanisms of estradiol insensitivity in the female squirrel monkey, 1993
Ward, Doris Juanita
1990-1999
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 E2 17S 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 E2-17 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-17 position. This enzyme could in effect reduce estrogenicity by masking the C-17 hydroxyl group necessary for activity.
text
application/pdf
1993-05-01
dissertation
Doctor of Philosophy (PhD)
Clark Atlanta University
School of Arts and Sciences, Biology
Musey, Paul I.
Georgia--Atlanta
http://hdl.handle.net/20.500.12322/cau.td:1993_ward_doris_j
