The Metabolic Clearance Rate and the Production Rate of Estradiol in Sexually Immature and Adult Female Rhesus Monkeys*

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Abstract
The blood MCR of estradiol (MCRE2) was measured in 34 experiments with 10 adult (4.7–8.2 kg) and 13 prepubertal (1.8–3.0 kg; 13–23 months old) female rhesus monkeys using the constant infusion technique. Twenty-six of the studies were performed using an adult and an immature animal simultaneously. Twenty-four of the studies were performed in pentobarbital-anesthetized animals, while the remainder used conscious animals restrained in primate chairs. The blood MCRE2 in the adult female was 167.5 ± 9.5 liters/day (mean ± SE; n = 14) or 27.5 ± 1.4 liters/day·kg BW, and was not altered by anesthesia, stage of the menstrual cycle, amenorrhea of more than 60 days duration, or the site of origin of the blood used to calculate the MCR (radial artery, femoral artery, femoral vein, or saphenous vein). While the absolute MCRE2 in the immature animal (either anesthetized or conscious) was less than that in the adult, when corrected for body weight, the relative MCRE2 (in liters per day/kg BW) of the conscious immature animal was double that seen in the adult [48.4 ± 5.2 (n = 6) vs. 27.5 ± 1.4 (n = 14)]. Anesthesia caused a profound depression of the MCRE2 in the immature animal, which could be prevented if the body temperature of the animal was maintained at 37 C during the prolonged period of anesthesia. The production rate of estradiol (PRE2) was calculated as the product of the serum estradiol concentration (in micrograms per liter; measured by RIA techniques) and the plasma MCRE2 (blood MCRE2 × 1 – hematocrit). In the adult animals, the PRE2 ranged from 1.9–35.5 μg/day, and was lowest in the amenorrheic animals and highest during the late follicular phase. The PRE2 in the immature animals ranged from unmeasurable to 1.7 μg/day, averaging 0.7 ± 0.2 μg/day (n = 12) in those animals where it could be measured. These data support the hypothesis that the low circulating estradiol levels in the immature animal are the consequence of a low PRE2 coupled with a high MCRE2(J Clin Endocrinol Metab56: 979, 1983)