SUMMARY 1. A study is presented of the pattern of metabolites in the urine of the rabbit following the injection of progesterone labelled with tritium and with carbon-14. 2. It is shown that, in the conditions of this experiment, no significant loss of tritium occurs by exchange when progesterone, generally labelled with tritium, is injected. 3. In the rabbit, the great majority of urinary metabolites of progesterone are in the conjugated form. 4. The distribution of radioactive metabolites in the acid, neutral, water and phenolic fractions (see p. 301) of the urine shows a consistent pattern in pregnant and non-pregnant females, and in males, over a wide range of doses. The acid fraction contains the most radioactive material. 5. Following the injection of a mixture of progesterone-16α-3H and progesterone-4-14C, no evidence could be found for the presence of 16α-hydroxy-metabolites in any of the urine fractions. 6. The presence of 20α-hydroxypregn-4-en-3-one as a metabolite of administered progesterone is confirmed. Evidence is presented to show that it is an intermediate product in the conversion of progesterone to pregnanediol in the rabbit. 7. The metabolism of progesterone in the rabbit is compared with that in man, and the significance of the differences found is discussed.

After injection of [4-14C]progesterone into rabbits, 62% of the radioactivity recovered from the urine after hydrolysis is extractable from ether into sodium bicarbonate solution. Treatment of these acidic metabolites with potassium borohydride, followed by sodium bismuthate, yields neutral material which can be separated into three zones by thin-layer chromatography. The most polar zone, accounting for 61 % of the radioactivity recovered from the plate, consists of epimers of 3,6-dihydroxyandrostan-17-al.