Evidence for the existence of a C25-sesterterpene pathway of steroidogenesis not involving cholesterol as an obligatory intermediate.
Previous in vitro studies had indicated the possibility of steroidogenesis through a C25-sesterterpene pathway in which squalene and cholesterol are not required as obligatory intermediates. To investigate whether such a pathway exists in vivo, the precursor role of [7-3H]23,24-dinor-5-cholene-3 beta,20-diol in the in vivo formation of cortisol by the guinea pigs was studied. The [3H]23,24-dinor-5-cholene-3 beta,20-diol was synthesized by reacting [3H]pregnenolone acetate with a Grignard reagent. The product was purified by chromatography and its radiochemical purity was established by the isotope dilution technique. In the first experiment a total of 134 X 10(6) dpm of [3H]23,24-dinor-5-cholene-3 beta,20-diol was injected subcutaneously into three guinea pigs. Urine was collected for 8 days and was pooled. Only 12% of the administered dose was excreted in the urine. The urine was extracted and a neutral extract (3 X 10(6) dpm) was obtained. From this extract 2.3 mg of cortisol containing 2.9 X 10(4) dpm was isolated. Radiochemical purity of the isolated cortisol was established by the isotope dilution technique. Radiochemical purity was further confirmed by conversion to cortisol 21-acetate and subsequently to 11 beta-hydroxyandrost-4-ene-3,17-dione and recrystallization to constant specific activity. The results of this experiment were confirmed by repeating the experiment with a higher specific activity [3H]23,24-dinor-5-cholene-3 beta,20-diol. These results indicate that the C25-sesterterpene pathway is a possible in vivo alternate pathway of steroidogenesis, not involving either squalene or cholesterol as obligatory intermediates.
D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000096:biosynthesis*; D008954:Models, Biological; D011283:Pregnenes / Q000378:metabolism; D011284:Pregnenolone / Q000378:metabolism*
D011283:Pregnenes; C007501:20-methylpregn-5-ene-3,20-diol; D011284:Pregnenolone; D002784:Cholesterol; D006854:Hydrocortisone