Effect of oestrogen on gonadotrophin release in stumptailed monkeys (Macaca arctoides) treated chronically with an agonist analogue of luteinizing hormone releasing hormone

Abstract

Nine adult female stumptailed monkeys (Macaca arctoides) treated chronically with daily s.c. injections of D-Ser(But)6,des-Gly10,Proethylamide9, luteinizing hormone releasing hormone (LH-RH agonist) to inhibit ovulation, were tested for their ability to respond to an oestrogen provocation test (positive feedback). On two occasions during treatment with the LH-RH agonist (first test between 10 and 35 weeks after treatment had started; second test between 30 and 60 weeks after) the animals were given an i.m. injection of 50 micrograms oestradiol benzoate/kg in arachis oil. Controls were tested between days 1 and 5 of the normal cycle. In the control monkeys oestrogen induced a clear rise in LH and FSH concentrations in the blood, with highest values between 48 and 60 h after treatment. In marked contrast, none of the animals treated with LH-RH agonist showed this pattern of response. In the first test, five of the nine monkeys showed no rise in LH while in the remaining animals the response was diminished or delayed, and in the second test all none failed to show a significant rise in LH. In all agonist-treated monkeys oestrogen failed to cause an FSH rise in either test. Thus, chronic treatment with LH-RH agonist in the monkey either abolishes, diminishes or delays the oestrogen-induced LH surge. Since, in the primate, oestrogen appears to release LH by acting directly on the pituitary gland exposed to pulses of LH-RH from the hypothalamus it appears that the LH surge is inhibited primarily because the pituitary gland has been exposed to prolonged stimulation by the agonist.