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

Department of Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261

Address requests for reprints to Dr. Julane Hotchkiss, Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston, Department of Physiology and Cell Biology, UTMSH, P.O. Box 20708, Houston, Texas 77025.

The blood MCR of estradiol (MCR_E2) 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 MCR_E2 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 MCR_E2 in the immature animal (either anesthetized or conscious) was less than that in the adult, when corrected for body weight, the relative MCR_E2 (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 MCR_E2 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 (PR_E2) was calculated as the product of the serum estradiol concentration (in micrograms per liter; measured by RIA techniques) and the plasma MCR_E2 (blood MCR_E2 x 1 – hematocrit). In the adult animals, the PR_E2 ranged from 1.9–35.5 µg/day, and was lowest in the amenorrheic animals and highest during the late follicular phase. The PR_E2 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 PR_E2 coupled with a high MCR_E2(J Clin Endocrinol Metab 56: 979, 1983)

^* A preliminary report of these data was presented at the 64th annual meeting of the Endocrine Society, 1982 (Abstract 149). This work was supported by Grant HD-14166 from the NICHHD.

Received October 4, 1982.

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