The in vivo metabolism of [3H]progesterone was studied in anesthetized female rhesus monkeys during either the early follicular phase or the midluteal phase of the menstrual cycle. An iv infusion of [3H]progesterone was given at a constant rate, and blood samples were obtained from catheters placed in the hepatic, renal, jugular, arm, and uterine veins and also in the femoral artery. The MCR of progesterone was 321 ± 14 (SE) liters/day. The MCR of progesterone in three dexamethasonetreated animals was 197 ± 15 (SE) liters/day. Tissue extractions of [3H]progesterone, calculated from the arteriovenous difference in blood concentrations, did not differ statistically between the follicular and luteal phases, except in the uterine extractions. The mean (±SE) extractions were: splanchnic, 94.5 ± 2.9%; renal, 14.6 ± 3.5%; head, 24.2 ± 1.5%; and arm, 48.1 ± 2.3%. The uterine extraction of progesterone was significantly (P = 0.001–0.005) higher in the early follicular phase [37.0 ± 7.8% (SE)] than in the luteal phase [14.9 ± 5.2% (SE)]. The tissue conversions of these organs systems of [3H]progesterone to 20α-hydroxypregn-4-en-3-one and 5α-pregnane-3, 20-dione were measured but could not account for more than 10% of the peripheral conversion of progesterone to 20α-hydroxypregn-4-en-3-one and 30% of the peripheral conversion of progesterone to 5α-pregnane-3, 20-dione. With the use of previously reported values for organ blood flows, the organ contributions to the overall MCR of progesterone were calculated, and it is estimated that approximately 65% of the metabolic clearance of progesterone in the monkey is due to splanchnic clearance. It is concluded that the splanchnic bed is the major area of the metabolic clearance of progesterone in the monkey, but that the extraction of progesterone by other tissues is appreciable. Since the phase of the menstrual cycle of the rhesus monkey influences uterine extraction, uterine metabolism may thus be significant in the tissue response to progesterone.
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