Enhanced hypothalamic dopaminergic inhibition of LH, TSH and GH release in patients with pathological hyperprolactinaemia

Abstract

Abstract. Recent studies have suggested that patients with prolactinomas have a defect in the central regulation of prolactin (Prl) release but it is not clear whether the defect results from a true loss of hypothalamic dopamine activity or from a functional inability of inherent dopaminergic inhibition to be mediated effectively. We have studied this question by the use of monoiodotyrosine (MIT, 1 g orally), a specific inhibitor of central dopamine synthesis to remove dopaminergic inhibitory control of Prl release in 10 normal ovulating women, 8 women on oral contraceptive steroids (OC) and 8 patients with pathological hyperprolactinaemia (PHP). LH, TSH and GH were also measured during the study in view of recent reports suggesting that dopaminergic mechanims may be involved in modulating their secretion. Subjects on OC had a significantly higher (P < 0.05) mean basal Prl (353 ± 34 vs 280 ± 26 mIU/l) and a significantly greater (P < 0.05) peak response (incremental change 2270 ± 300 mIU/l to MIT than normal controls (1320 ± 220 mIU/l). Patients with PHP had a highly significantly blunted (P < 0.001) Prl response (incremental change 290 ± 95 mIU/l) compared to controls. MIT administration caused a significant increase in LH (P < 0.05), TSH (P < 0.01) and GH (P < 0.01) in patients with PHP but not in normal or OC-treated subjects. The augmented Prl response of subjects on OC is consistent with an increase in dopaminergic inhibitory control of Prl release. The lack of Prl response in subjects with PHP is indicative of a functional loss of dopaminergic control. Whilst the levels of dopamine activity in normal controls and in subjects on OC are unimportant in regulating LH, TSH and GH release, the use of MIT has revealed a significant inhibitory effect of dopaminergic mechanisms in modulating the release of these hormones in patients with PHP. The response of these hormones in patients with PHP is consistent with a supraphysiological degree of hypothalamic dopamine activity. We conclude that the defect in the control of Prl release in patients with PHP results from an inability of dopaminergic inhibition to be mediated effectively.