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Metabolic Clearance Rates and the Interconversion Factors of Estrone and Estradiol-17βin the Immature and Adult Female Rat
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1970
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Adult Female RatGynecologyFemale Reproductive FunctionReproductive EndocrinologyMetabolic Clearance RateInterconversion FactorsPublic HealthHuman MetabolismNuclear MedicineSteroid MetabolismAnimal PhysiologyMetabolic Clearance RatesBiochemistryEndocrine MechanismTotal RadioactivityMetabolomicsEndocrinologyPharmacologyInfusion RatesPhysiologyMetabolismMedicine
The metabolic clearance rate (MCRp) of estrone (E1) and estradiol-17β(E2) has been measured in adult and immature female Wistar R rats by long-term intravenous infusions with tritium-labeled hormones. Plasma radioconcentrations were shown tobe constant at the end of 3- or 4-hr infusions for total radioactive metabolites and for isolated precursor (infused hormone) and product of interconversion. Fractional turnover time of total radioactive metabolites in plasma was constant throughout the range of infusion rates, starting from 0.5 up to 920 ng/hr for E2-6,7-3H in adult, from 0.26 up to 677 ng/hr for E2-6,7-3H in immature andfrom 5 up to 2000 ng/hr for E1-6,7-3H in adult animals. MCRpEl was equal to 570±35 (SD) ml/hr in adult, and 161 ml/hr in one groupof immature animals. MCRpE2 was equal to 676 ±70 ml/hr in adult, and was independent of the ratesofinfusionranging from 4.9 to 703 ng/hr. In immature MCRpE2 increased slowly with increasing rates of infusion and the correlation (p<0.05) was equal to 323.5+0.28 I ml/hr, where I is the rate of infusion in ng/hr. Blood interconversion factors (ρBB) were calculated from the equilibrium concentrations of E1-6,7-3H and E2-6,7-3H in each type of infusion. Hence ρBBE1E2 was equal to 8–8.8% in adult and 21% in immature animals; ρBBE2E1 was equal to 14–20% in adult and 18–33% in immature animals. When related to body size (weight¾), MCRpE2 in adult and in immature female rats were similar to reported values in women. MCRpE1 was relatively lower, on a similar basis of comparison. From uptake of total radioactivity by red cells and MCRp, an approximation of MCRB (in ml of whole blood/hr) was obtained, which was equal to 1100 ml/hr for MCRBE2 and 900 ml/hr for MCRBE1. Hence, a minimal extrahepatic clearance of 20–40% of estrogen total clearance rate is likely to occur, which compares with observations reported in the human. (Endocrinology87: 874, 1970)