The Influence of Progesterone on the Conversion of 17-Hydroxyprogesterone to Testosterone in the Mouse Testis1
Keishi Matsumoto, Damodar K. Mahajan, Leo T. Samuels
Abstract
Keishi Matsumoto, Damodar K. Mahajan, Leo T. Samuels
Abstract
Progesterone-3H and 17-hydroxyprogesterone- 14C were incubated with mouse testis homogenates and the distribution of each isotope in 17-hydroxyprogesterone,2 androstenedione and testosterone when the two precursors were present in various ratios were compared with the amounts when each precursor was present alone. The presence of equal amounts of progesterone and 17-hydroxyprogesterone caused a small but significant reduction in 17-hydroxylase activity. The rate at which 17-hydroxyprogesterone, or 17- oxy radical formed from progesterone, was converted to C19 steroids was essentially unaffected by the presence of added 17-hydroxyprogesterone, probably because of the close association of active sites of the 17-hydroxylase and lyase. The rate of splitting of the added 17-hydroxyprogesterone, however, was markedly inhibited by the presence of progesterone. The inhibition was probably competitive as previously reported for rat testes. The results indicated that the active site of the 17β-dehydrogenase was not closely associated with the lyase. At higher levels of either precursor alonethe 17β-dehydrogenase approached saturation, but the inhibition of lyase activity by progesterone left the 17β-dehydrogenase unsaturated and a higher proportion of the smaller amounts of androstenedione formed was converted to testosterone. (Endocrinology94: 808, 1974)
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Progesterone-3H and 17-hydroxyprogesterone- 14C were incubated with mouse testis homogenates and the distribution of each isotope in 17-hydroxyprogesterone,2 androstenedione and testosterone when the two precursors were present in various ratios were compared with the amounts when each precursor was present alone. The presence of equal amounts of progesterone and 17-hydroxyprogesterone caused a small but significant reduction in 17-hydroxylase activity. The rate at which 17-hydroxyprogesterone, or 17- oxy radical formed from progesterone, was converted to C19 steroids was essentially unaffected by the presence of added 17-hydroxyprogesterone, probably because of the close association of active sites of the 17-hydroxylase and lyase. The rate of splitting of the added 17-hydroxyprogesterone, however, was markedly inhibited by the presence of progesterone. The inhibition was probably competitive as previously reported for rat testes. The results indicated that the active site of the 17β-dehydrogenase was not closely associated with the lyase. At higher levels of either precursor alonethe 17β-dehydrogenase approached saturation, but the inhibition of lyase activity by progesterone left the 17β-dehydrogenase unsaturated and a higher proportion of the smaller amounts of androstenedione formed was converted to testosterone. (Endocrinology94: 808, 1974)
Key concepts: Androstenedione, Hydroxyprogesterone, Internal medicine, Endocrinology, Testosterone (patch), Chemistry, Dehydrogenase, Lyase