Metabolism of progesterone in the pregnant sheep near term: identification of 3 beta-hydroxy-5 alpha-pregnan-20-one 3-sulfate as a major metabolite.
Two pregnant ewes near term were given a single injection of progesterone-4-14C via the left jugular vein, and serial blood samples were taken from the right jugular vein at 5 min intervals over a period of 40 min. Radioactive steroids in the plasma were separated into unconjugated and conjugated fractions which were further isolated and analysed by established methods. The injected hormone was rapidly metabolized with a half-life of approximately 10 min and metabolic clearance rate about 3.5 liters min. The bulk of the metabolites was found in the sulfate fraction from which a major metabolite was identified as 3 beta-hydroxy-5 alpha-pregnan-20-one. From the unconjugated fraction, 20 alpha-hydroxy-pregn-4-en-3-one, a known minor metabolite was also isolated. No radioactive estrogens were found. It is concluded that a major portion of circulating progesterone in the pregnant ewe near term is cleared by 5 alpha-reduction of ring A, followed by sulfo-conjugation.
D000818:Animals; D002250:Carbon Radioisotopes; D005260:Female; D007553:Isotope Labeling; D011247:Pregnancy; D011270:Pregnancy, Animal; D011278:Pregnanes / Q000031:analogs & derivatives*; D011280:Pregnanolone / Q000031:analogs & derivatives* / Q000097:blood; D011374:Progesterone / Q000097:blood*; D012756:Sheep; D014316:Tritium
D002250:Carbon Radioisotopes; D011278:Pregnanes; D014316:Tritium; D011374:Progesterone; D011280:Pregnanolone