Pituitary sensitivity to gonadotrophin releasing hormone after hyperprolactinaemia induced with neuroleptics and domperidone in the rat.

Abstract

The effect of hyperprolactinaemia induced by dopamine-antagonist drugs on pituitary responsiveness to gonadotrophin releasing hormone (Gn-RH) and on plasma LH levels has been investigated in intact and ovariectomized rats. The animals were pretreated with haloperidol, pimozide or domperidone and the sensitivity of isolated pituitary glands to pulses of Gn-RH were tested using a perifusion system. Trunk blood, collected at the time of killing, was assayed for plasma LH and prolactin. In addition, a direct effect of the drugs on pituitary responsiveness to Gn-RH was investigated by perfusing pituitary glands taken from untreated, pro-oestrous rats in medium containing the dopamine antagonists. The pituitary responsiveness was significantly impaired in intact rats after treatment with each of the drugs whereas no effect was observed in pretreated ovariectomized rats. None of the drug treatments altered levels of circulating LH. High concentrations of the drugs present in the perifusion medium also inhibited pituitary responsiveness although it is not known whether the concentrations of the drugs present in the pretreated animals would exert a similar effect. The results suggest that short-term hyperprolactinaemia impairs pituitary responsiveness through a modulation of ovarian steroid secretion and that Gn-RH release is not altered. Treatment with domperidone exhibited similar effects on the parameters measured here to those caused by the two neuroleptics, indicating that this novel anti-dopaminergic drug is acting in a similar manner.