Role of dopamine in the inhibitory control of growth hormone and prolactin release by gastrin-releasing peptide

Abstract The ability of gastrin-releasing peptide to inhibit the release of growth hormone and prolactin by a hypothalamic mechanism has been previously reported. To determine whether or not these effects involved the hypothalamic dopaminergic neurons, ovariectomized female rats were pretreated with the dopamine receptor blocker, pimozide (0.6 mg/kg, SC), or the diluent 35 min prior to administration of gastrin-releasing peptide (2 μg in 2 μl 0.9% NaCl) into the third ventricle. The elevation in plasma growth hormone in response to growth hormone-releasing factor (GRF; 1 μg/kg, IV) was blocked by gastrin-releasing peptide as previously reported following pretreatment with the diluent, but occurred following the injection of pimozide, reversing the inhibitory action of gastrin-releasing peptide. Some control animals that were injected with the pimozide vehicle exhibited elevated plasma prolactin levels compared to levels in uninjected controls. Gastrin-releasing peptide significantly lowered plasma prolactin concentrations in this group of animals. As expected, plasma prolactin levels were elevated following pimozide treatment due to the removal of inhibitory dopaminergic control. Prolactin concentrations were unresponsive to gastrin-releasing peptide treatment in this paradigm and remained elevated throughout the 40-min duration of sampling. We interpret these data to indicate that gastrin-releasing peptide exerts its inhibitory actions on the release of growth hormone and prolactin through a dopaminergic mechanism. Gastrin-releasing peptide may elicit the release of dopamine from tuberoinfundibular neurons, which a) stimulates release of somatostatin, thus inhibiting the release of growth hormone, and b) reaches the pituitary directly via the hypophysial portal vessels to inhibit the release of prolactin from the lactotropes.