Drug-induced hyperprolactinaemia and discharges of luteinizing hormone evoked by oestrogen in ovariectomized rhesus monkeys.
Ovulatory failure associated with hyperprolactinaemia has been attributed to the inability of oestrogen to evoke a preovulatory discharge of gonadotrophins. This hypothesis was tested in ovariectomized rhesus monkeys rendered hyperprolactinaemic by treatment with two dopamine antagonists, domperidone, a compound reported not to cross the blood-brain barrier in rats, and sulpiride, a drug with known actions on both pituitary and central dopaminergic receptors. An artificial surge of oestrogen similar to that observed at mid-cycle in intact monkeys was obtained with subcutaneous capsules filled with oestradiol-17 beta. Treatment with either drug increased prolactin concentrations to 1.0 i.u./l or more compared with control values of 0.1-0.3 i.u./1. In the presence of these greatly increased prolactin levels, a normal discharge of LH, indistinguishable from that observed in control animals, was provoked by oestrogens in all but one drug-treated monkey. Furthermore, neither the basal (pre-oestrogen) level of LH nor the negative feedback action of oestrogen was consistently altered in hyperprolactinaemic monkeys. Administration of progesterone or 17 alpha-hydroxyprogesterone to simulate more closely the conditions observed in intact animals during the periovulatory period did not alter the LH discharge induced by oestrogen in animals treated with domperidone. The present results suggest that the high levels of prolactin brought about by dopaminergic blockade do not affect the positive feedback action of oestrogen. Furthermore, low levels of progestins do not sensitize the hypothalamic-pituitary axis towards an inhibitory action of prolactin on oestrogen-induced LH release. The rhesus monkey thus differs from other species, including man, in which artificially induced hyperprolactinaemia may impair or abolish the positive feedback action of oestrogen.
D000818:Animals; D002369:Castration; D004294:Domperidone / Q000494:pharmacology; D004958:Estradiol / Q000032:analysis; D004967:Estrogens / Q000502:physiology*; D005260:Female; D007986:Luteinizing Hormone / Q000378:metabolism*; D008253:Macaca mulatta; D011388:Prolactin / Q000097:blood*; D013469:Sulpiride / Q000494:pharmacology
D004967:Estrogens; D004958:Estradiol; D004294:Domperidone; D013469:Sulpiride; D011388:Prolactin; D007986:Luteinizing Hormone