Role of peripheral and central aromatization in the control of gonadotrophin secretion in the male sheep

Abstract

Both testosterone and its aromatized metabolite, oestradiol-17b, 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 g kg –1 per 24 h for 3 days) were given four injections of fadrozole (i.m; 500 g 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-17b 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 g kg –1 per day). After two weeks, the same two doses of fadrozole were infused intravenously instead of intracerebrally. Central infusion of fadro-zole 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.