Steroidogenesis in the monkey testis: relationship of enzyme organization to endogenous steroids, steroidogenesis and gonadotropin treatment.
To explore testicular factors which determine steroidogenesis, circulating and intratesticular steroid levels were measured and in vitro steroidogenesis in testicular mines and microsomes was investigated using adult rhesus monkeys before and after treatment with pharmacological doses of hCG or hCG together with hMG. After gonadotropin treatment serum and intratesticular levels of 17 alpha-hydroxyprogesterone as well as end product testosterone were markedly elevated. Dynamic studies revealed that 17 alpha-hydroxyprogesterone produced from pregnenolone was partly metabolized to C19-steroids but almost no 17 alpha-hydroxyprogesterone produced from progesterone was utilized by C17-20 lyase. Androstenedione levels increased in serum after both treatments and were elevated in testis tissue after hCG treatment. Androstenedione accumulated in vitro during incubation of untreated and hCG-treated testes with [3H]pregnenolone and [14C]progesterone. The major portion of the accumulated androstenedione was produced from pregnenolone through dehydroepiandrosterone rather than through 17 alpha-hydroxyprogesterone, indicating differential availability of androstenedione to 17 beta-hydroxysteroid oxidoreductase according to its origin. The 3H/14C ratio in product androstenedione was much greater than the ration in product testosterone in both untreated and hCG-treated testis; in testes of animals treated with hCG together with hMG, the ratios in both products were closely linked. Among the enzymes examined, 17 alpha-hydroxylase and C17-20 lyase activities for 5-ene-C21-steroids were increased and 17 beta-hydroxysteroid oxidoreductase activity were decreased by gonadotropin treatment. Our findings confirm the phenomenon of unequal substrate availability to enzymes depending upon the provenance of the substrate and demonstrate that gonadotropin(s) change substrate availability as do direct changes in enzyme activities. The unequal substrate availability validates the assumption, previously proposed by others, that microsome enzymes have an organized arrangement as enzyme complexes.
D000818:Animals; D001711:Biotransformation; D002474:Cell-Free System; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D008861:Microsomes / Q000378:metabolism; D011284:Pregnenolone / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*; D013737:Testis / Q000201:enzymology / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism*; D013997:Time Factors
D006063:Chorionic Gonadotropin; D013256:Steroids; D013739:Testosterone; D011284:Pregnenolone