Effects of chronic treatment with oestrogen, an oestrogen antagonist and a potent luteinizing hormone releasing hormone agonist analogue on pituitary responsiveness to luteinizing hormone releasing hormone in the rat.
The rise in gonadotrophin release which occurs after ovariectomy is caused by steroid withdrawal resulting in an enhanced pituitary responsiveness to LH releasing hormone (LHRH) associated with increased LHRH release and pituitary LHRH binding. The effects of oestrogen replacement after ovariectomy and chronic treatment of intact rats with an oestrogen antagonist, tamoxifen, on LH release and in-vitro pituitary responses to LHRH have been investigated. Capsules containing crystalline oestradiol, implanted at the time of ovariectomy, completely inhibited the rise in LH release although pituitary responsiveness was greater after 10 days in the oestrogen-treated rats than in untreated ovariectomized controls. On day 4 after ovariectomy pituitary responses to LHRH were comparable in both treated and untreated groups although in both groups the responses were greater than those measured in intact dioestrous rats. Treatment with tamoxifen over a 4-day period also augmented pituitary responsiveness but only at the lowest dose (0.5 mg/kg); no effect on serum LH concentrations was observed. Higher doses of the antagonist (1 and 2 mg/kg) did not affect pituitary responses, although the highest dose did cause a significant rise in serum LH. Treatment with a daily dose of 50 ng [D-Ser(But)6]LHRH(1-9)nonapeptide-ethylamide, starting on the day of ovariectomy, markedly attenuated the LH responses to LHRH ex vivo at days 2, 4 and 10 after ovariectomy. In contrast, the analogue treatment did not abolish the rise in LH release but this was proportionately less than in controls.
D000818:Animals; D002064:Buserelin / Q000494:pharmacology*; D002369:Castration; D004343:Drug Implants; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013629:Tamoxifen / Q000494:pharmacology*
D004343:Drug Implants; D013629:Tamoxifen; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone; D002064:Buserelin