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J. Y. F. Paterson, F. A. Harrison, E. L. Sheldrick and R. B. Heap

Summary. When [3H]progesterone is infused intravenously into ewes, blood 20α-dihydroprogesterone (20α-diHP) becomes labelled and the changes in [3H]20α-diHP activity with time are clearly related to that of [3H]progesterone. Concentrations of 20α-diHP in blood have now been estimated for these experiments. During the infusion, the specific radioactivity of 20α-diHP at steady state was only 53% of the specific radioactivity of progesterone, indicating that 20α-diHP was produced other than by C-20 reduction of secreted progesterone. The change in blood concentration of 20α-diHP during pregnancy in ewes suggests that the placenta is its source.

[3H]20α-dihydroprogesterone was infused into pregnant ewes and the specific radioactivity of 20α-diHP measured during and after infusion. Together with information from earlier experiments when [3H]progesterone was infused, there is now sufficient data to estimate, without constraint, the parameters of a four-pool model describing the distribution and metabolism of progesterone and 20α-dyhydro-progesterone in sheep.

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J. Y. F. Paterson, Cecelia A. Bedford, F. A. Harrison and R. B. Heap

Summary.

The rates of metabolism of progesterone and 20α-dihydroprogesterone (20α-diHP) in sheep have been measured during and after the infusion of tracer amounts of [3H]progesterone. There were significant differences in the blood concentration of [3H]progesterone between experiments, but these were not attributable to the stage of gestation or to the difference between pregnant and non-pregnant animals. The mean (±S.E.M.) metabolic clearance rate of progesterone was 3·277 ± 0·239 litres blood/min.

The simplest model of the distribution of progesterone was one containing two pools, V1[P] and V2[P], where [P] is the blood concentration of progesterone, and in 23 experiments on 7 sheep the mean pool dimensions were 7·8[P] μg and 70[P] μg, respectively. This model was developed to include the formation of 20α-diHP from progesterone. Progesterone appeared to be the major source of 20α-diHP, though this did not seem to be an obligatory metabolite. The parameters obtained gave comparably low residual deviations for both labelled steroids and were consistent with other observations made on progesterone clearance.