DISTRIBUTION AND METABOLISM OF MATERNAL PROGESTERONE IN THE UTERUS, PLACENTA, AND FETUS DURING RAT PREGNANCY

This study examined the in vivo distribution and metabolism of maternal progesterone (P-4) in the rat uterus at Day 16 of pregnancy, i.e., the time of maximal P-4 secretion, and at Day 22, one day prior to parturition. Arterial and uterine venous blood samples were collected at 20-min intervals from rats (n = 5 per group) infused with [H-3]-P-4 for 2 h. Placentas, fetuses, and uterine tissue (myometrium and decidua) were obtained just prior to the end of the infusion; and total tritium, [H-3]-P-4, and lipid-soluble and water-soluble metabolite concentrations were determined in all blood and tissue samples. Irreversible extraction of P-4 by the uterus and its contents was 54.2 +/- 6.0% (mean +/- SEM) on Day 16, and this was at least maintained to Day 22 (64.7 +/- 7.4%). Because uterine blood now increases dramatically over this period, the maintenance of high uterine P-4 extraction is likely to have contributed partly to the 41% rise in the metabolic clearance rate of P-4 between Day 16 (147 +/- 16 ml/min per kg) and Day 22 (207 +/- 13 ml/min per kg). Uterine tissue levels of [H-3]-P-4 exceeded (1.6-fold) those in arterial blood on Day 16, but this difference was not evident at Day 22. In contrast, the concentration of [H-3]-P-4 in the placenta was lower than that in arterial blood at Day 16 (66% lower) and Day 22 (25% lower), even though total tritium concentrations were similar at these sites. [H-3]-P-4 was also lower in fetal tissue compared with maternal arterial blood on both days of pregnancy. Uterine extraction of P-4 primarily reflected conversion to lipid-soluble products, since tritium levels increased only in this fraction during passage of maternal blood across the uterus. This conversion of P-4 to lipid-soluble metabolites most likely occurred in uterine and placental tissues, since both contained relatively high levels of these metabolites, consistent with previous in vitro studies. Comparison of changes in [H-3]-P-4 and endogenous P-4 concentrations from arterial to uterine venous blood indicates that tissues within the uterus are a source of de novo P-4 secretion. Although this secretion is of minor significance to the total maternal P-4 pool, it is potentially important as a source of active hormone within the uterus. In conclusion, these data show that metabolism of P-4 by the uterus and its contents is extensive during late pregnancy in the rat. The distribution pattern of [H-3]-P-4 and its [H-3]-labeled metabolites indicates that retention of unmetabolized [H-3]-P-4 by uterine tissue declines toward term, and suggests that placental metabolism limits transfer of maternal P-4 to the fetus.