Dynamics of progesterone metabolism in the pseudopregnant rat

The characteristics of the disappearance of progesterone and 20 alpha-dihydroprogesterone from blood were examined in rats made pseudopregnant by administration of gonadotrophins. Measurement of the disappearance of [3H]progesterone from blood indicated that progesterone metabolism can be represented by a two-compartment model in this animal preparation. The disappearance of [3H]progesterone from blood was described by two half-lives of 0.5 and 11.7 min. The metabolic clearance rate for this steroid was 2.9 litre/day, equivalent to a production rate of 3.9 mumol/day. The initial volume of distribution of the injected [3H]progesterone was 5.0 ml, a volume similar in size to the expected plasma volume. The total volume of distribution of [3H]progesterone (i.e. 'inner' and 'outer' pools) was in the range 24.8-35.4 ml. The disappearance of endogenous progesterone from the blood of pseudopregnant rats after vascular isolation of the ovaries showed two half-lives of 1.1 and 11.4 min respectively. The disappearance of a product of reductive metabolism of progesterone, 20 alpha-dihydroprogesterone, was apparently uniphasic, with a half-life of 41.3 min.