Specificity of the direct effect of an LHRH agonist on testicular 17-hydroxylase but not on 5 alpha-reductase activity in hypophysectomized adult rats.
The direct effect of treatment with a potent LHRH agonist on testicular steroidogenesis was studied by incubation of radioactive steroids with a testicular homogenate or with a suspension of interstitial cells obtained following 7 days of treatment of adult hypophysectomized male rats. The animals received [D-Ser(tBu)6,des-Gly-NH2(10)]LHRH ethylamide (25 micrograms) administered 3 times a day, hCG (5 or 25 IU) once daily or a combination of both drugs. The metabolism of tritiated progesterone into delta 4-metabolites by a suspension of interstitial cells was markedly reduced by treatment with the LHRH agonist (LHRH-A) alone or following combined treatment with hCG and LHRH-A. No formation of 5 alpha-reduced steroids was detected in the medium following incubation with testicular homogenate or interstitial cells. Similar findings were obtained by measurement of testicular steroid content. The present data demonstrate that the direct effect of the LHRH agonist is limited to the Leydig cells on 17-hydroxylase activity. This inhibitory effect is reflected by an accumulation of testicular pregnenolone and progesterone content and a marked inhibition of progesterone metabolism into delta 4-androgens. However, no stimulation of 5 alpha-reductase, an enzyme localized in seminiferous tubules, could be detected. Such data show clear differences between the direct and the pituitary-mediated effects of treatment with LHRH agonists on testicular steroidogenesis. While the LHRH agonist administered at high doses in the rat can directly inhibit 17-hydroxylase activity, the stimulatory effect on 5 alpha-reductase activity is regulated by another mechanism.
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D000818:Animals; D002064:Buserelin / Q000494:pharmacology*; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D007985:Leydig Cells / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000502:physiology; D011284:Pregnenolone / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D012671:Seminiferous Tubules / Q000201:enzymology; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors; D013256:Steroids / Q000096:biosynthesis*; D013737:Testis / Q000187:drug effects* / Q000378:metabolism
D006063:Chorionic Gonadotropin; D013256:Steroids; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D011284:Pregnenolone; D010088:Oxidoreductases; D013254:Steroid 17-alpha-Hydroxylase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D002064:Buserelin