Sharma T P, Blache D, Blackberry M A, Martin G B
Faculty of Agriculture (Animal Science), The University of Western Australia, Nedlands, Australia.
Reprod Fertil Dev. 1999;11(4-5):293-302. doi: 10.1071/rd99084.
Both testosterone and its aromatized metabolite, oestradiol-17beta, are known to act centrally on the secretion of GnRH, but the major site of aromatization is not clear as aromatase activities are found in numerous tissues including brain and testis. Here, we tested the importance of central aromatization of testosterone using a non-steroidal aromatase inhibitor, fadrozole. To distinguish between testicular and non-testicular sites, five intact and five testosterone-infused castrated rams (600 microg kg(-1) per 24 h for 3 days) were given four injections of fadrozole (i.m.; 500 microg kg(-1)) at 48, 52, 64 and 68 h relative to the start of testosterone infusion. Control rams (n = 5) received vehicle only. Fadrozole treatment decreased plasma oestradiol-17beta concentrations and increased the LH pulse frequency in both intact rams and testosterone-treated castrates, suggesting that non-testicular sites of aromatization are important in the control of pulsatile LH secretion. To test the importance of central aromatization, intact rams (n = 5) were infused into the third ventricle with vehicle (artificial cerebrospinal fluid) or with fadrozole (20 and 200 microg kg(-1) per day). After two weeks, the same two doses of fadrozole were infused intravenously instead of intracerebrally. Central infusion of fadrozole did not affect plasma oestradiol concentrations but increased LH pulse frequency. Only the highest dose increased LH pulse frequency when infused intravenously. In conclusion, central aromatization is involved in the control of pulsatile LH secretion in male sheep.
已知睾酮及其芳香化代谢产物雌二醇-17β均可作用于GnRH的中枢分泌，但由于在包括脑和睾丸在内的众多组织中均发现有芳香化酶活性，所以主要的芳香化位点尚不清楚。在此，我们使用非甾体芳香化酶抑制剂法倔唑来检测睾酮中枢芳香化的重要性。为区分睾丸和非睾丸部位，对5只完整公羊和5只睾酮注入的去势公羊（每24小时600微克/千克，持续3天）在相对于睾酮注入开始的48、52、64和68小时给予4次法倔唑注射（肌肉注射；500微克/千克）。对照公羊（n = 5）仅接受赋形剂。法倔唑处理降低了完整公羊和睾酮处理的去势公羊的血浆雌二醇-17β浓度，并增加了LH脉冲频率，这表明非睾丸部位的芳香化在脉冲式LH分泌的控制中很重要。为检测中枢芳香化的重要性，对5只完整公羊经第三脑室注入赋形剂（人工脑脊液）或法倔唑（每天20和200微克/千克）。两周后，改为静脉内注入相同剂量的两种法倔唑而不是脑内注入。脑内注入法倔唑不影响血浆雌二醇浓度，但增加了LH脉冲频率。静脉内注入时只有最高剂量增加了LH脉冲频率。总之，中枢芳香化参与了雄性绵羊脉冲式LH分泌的控制。
