Ｈｅｘｅｓｔｒｏｌ　ｄｉｃａｐｒｙｌａｔｅのイヌ精巣におけるｔｅｓｔｏｓｔｅｒｏｎｅ産生に対する抑制機構

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  • Inhibitory mechanisms of H8 on testosterone production in canine testes.
  • Hexestrol dicaprylate ノ イヌ セイソウ ニ オケル t

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Inhibitory mechanisms of hexestrol dicaprylate (H8) on testosterone production in canine testes were studied. Testicular homogenate (100 mg) was incubated with 3H-H8 (10 nmol) for 2 h at 34 C. Following incubation, radioactive metabolites were extracted, isolated by TCL, and identified with the method of recrystallization. Approximately 30%of 3H-H8 was metabolized to 3H-hexestrol (H0) in testicular homo-genate.<BR>One hundred mg of the sliced testis was incubated with 1 IU hCG and 0.01-1μg of H8 or H0 for 12h at 34C in an atomosphere O2:CO2 (95:5%). Testosterone, pregnenolone and cyclic AMP content in the medium were determined by radioimmunoassay or competitive protein binding assay. Testosterone production in testicular tissue was stimulated by hCG. The addition of H0 markedly depressed the testosterone response of testis to hCG, while the addition of H8 weakly depressed it. Formations of cyclic AMP and pregnenolone were not affected by H0.<BR>Male dogs were injected with a single dose of H8 (2 or 20mg/kg). Each testis removed on the 90th day after H8 injection was homogenized, and incubated with 14C-pregnenolone. H8 treatment caused significant decreases in the convertion of pregnenolone to 4-androstenedione and testosterone, with the accumulation of dehydroepiandrosterone in vitro. By a high dose of H8, the accumulation of 17 α-hydroxypregnenolone also was observed.<BR>These results suggest that H8 after being hydrolyzed to H0 in testes directly inhibits the testicular steroidogenesis, and they will also imply that the principle site of H8 inhibition is located at the metabolic pathway of dehydroepiandrosterone to testosterone.

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