Restoration of the Prolactin Response to Sulpiride by Metergoline Administration in Hyperprolactinemic Patients

Abstract

Although metergoline (MCE) inhibits prolactin (Prl) secretion in normal and hyperprolactinemic subjects similarly to dopamine (DA) and DA agonists, several data suggest that it acts through a different mechanism, probably as a serotonin antagonist. To further evaluate its Prl-lowering effect, paired sulpiride (Sulp) tests (100 mg i.m.) were performed before and after acute MCE administration (4 mg by mouth 120 min before Sulp) in 10 normal women, while 30 hyperprolactinemic women with pituitary microadenoma and no Prl response to Sulp were studied before and after acute or chronic treatment with either MCE (8–12 mg/day for 1-3 months) or bromocriptine (CB-154) (2.5 mg 300 min before Sulp, or 5 mg/day for 1-2 months), or during DA infusion (5 μg/kg/min for 180 min, Sulp being injected at 120 min). MCE did not alter the Sulp-stimulated Prl release in normal subjects and induced, both after acute and chronic administration, a clear Prl response to Sulp in hyperprolactinemic patients, which did not differ from that occurring in normals. During DA infusion, Sulp induced a marked increase in serum Prl levels, as previously reported in hyperprolactinemic patients without evidence of pituitary tumor; this increase was significantly higher than that observed in normals and in MCE-treated hyperprolactinemic subjects. No Prl response to Sulp occurred in CB-154-treated patients. Basal Prl levels were significantly lowered by all treatments. Although the similarity of effects of MCE and DA on Sulp-induced Prl release might suggest that MCE acts by stimulation of DA receptors, this hypothesis is not supported by pharmacological nor by in vitro and in vivo endocrinological studies; such an action might perhaps be exerted by the drug indirectly via serotoninergic blockade or through hypothetical metabolites. Alternatively, MCE might induce a Prl increase after Sulp in hyperprolactinemic patients by restoring the response of the normal lactotropes, usually suppressed by a central dopaminergic