Fate of progesterone in the plasma and various tissues of anaesthetized rabbits

Studies on the metabolism of progesterone in rabbit plasma and tissues during constant infusion of [3H]progesterone revealed a gradual increase in the concentration of progesterone in plasma until a state of equilibrium was attained about 2 h after the start of infusion. The metabolic clearance rate of progesterone was 0.116 l/min and the turn-over time was 0.006 min/ml plasma. Under conditions of equilibrium, the concentration of radioactivity as well as that of labelled progesterone was higher in the tissues than in plasma. On a unit-weight basis, myometrium localized 6.6 nCi, Fallopian tube 5.5 nCi and vagina 6.1 nCi [3H]progesterone/g tissue. A higher concentration of progesterone, 16.5 nCi, was localized in the mammary gland tissue. Skin localized only 0.9 nCi progesterone and the lowest amount (0.34 nCi/ml) was found in plasma. The metabolism of progesterone in tissues differed from that in plasma. In plasma only 5.6% of the infused steroid was recovered as unconverted progesterone and the major amount was metabolized to polar compounds with smaller amounts of 5 alpha-pregnane-3,20-dione, 5 alpha-pregnan-3 beta-ol-20-one and 20 alpha hydroxypregn-4-en-3-one. In the myometrium and Fallopian tubes the major metabolites were 5 alpha-pregnan-3 beta-ol-20-one and 5 alpha-pregnane-3,20-dione respectively. In the vagina, like the myometrium, 5 alpha-pregnan-3 beta-ol,20-one was the major metabolite. 20 alpha-Hydroxypregn-4-en-3-one was the major identified metabolite of mammary gland tissue.