Pathways for androgen biosynthesis from [7α-3H]pregnenolone and [4-14C] progesterone by rat testis interstitium in vitro

Abstract 1. 1. Rat testis interstitial tissue, freed from tubule structures, and whole testis tissue were incubated with [7α- 3 H]pregnenolone and [4- 14 C]progesterone. Interstitial tissue was also incubated with [7α- 3 H]testosterone and [4- 14 C]androstenedione. Samples of the incubation media were withdrawn after various intervals of time, and the products isolated and identified. Their yields from the precursors were calculated and plotted against time. 2. 2. The product yield-time curves were interpreted on the basis that sequential maxima in isotope incorporation in the different products reflected the order in which the compounds occurred in the biosynthetic pathway. In this way it was deduced that under the conditions chosen, the preferred pathway for the formation of testosterone from pregnenolone was pregnenolone…progesterone…17α-hydroxyprogesterone…androstenedione…testosterone. 17α-Hydroxypregnenolone was not formed in significant amounts and other possible pathways appeared to be unimportant. 3. 3. Testosterone was invariably metabolised to further products, as yet unidentified, and therefore did not reach equilibrium with androstenedione. 4. 4. Possible explanations are offered for apparent discrepancies in the literature.