Prolactin Response to Dopamine Synthesis Inhibition Using Monoiodotyrosine in Subjects on Oral Contraceptives and Patients with Pathological Hyperprolactinemia

Monoiodotyrosine (MIT), a specific inhibitor of central dopamine synthesis, has been used to study dopaminemediated inhibitory control of PRL release in 10 normal women, 19 women on oral contraceptive steroids (OC), and 14 women with pathological hyperprolactinemia to test the hypothesis that while the mild hyperprolactinemia in OC subjects is under dopaminergic control, there is a loss of inhibitory control in subjects with pathological hyperprolactinemia. Of these latter patients, 6 had normal pituitary fossa on x-rays, and 8 had unequivocal radiological evidence of a pituitary tumor. Subjects on OC had a significantly higher mean basal PRL level (353 ± 34 vs. 280 ± 26 mIU/liter; P < 0.05) and a significantly greater response (740 ± 97% vs. 521 ± 84%; P < 0.05) to MIT compared to controls. Subjects on OC with normal basal PRL levels (<400 mIU/liter; n = 11) had a significantly greater integrated percentage change in response (P < 0.025) than the subgroup with elevated basal PRL level (>400 mIU/liter; n = 8). Subjects with pathological hyperprolactinemia had a significantly blunted incremental response (274 ± 73 vs. 1348 ± 221 mIU/liter; P < 0.005) and percentage response (13.4 ± 3.5% vs. 521 ± 84%; P < 0.001) to MIT compared with those of controls. The stimulated PRL responses in subjects with and without radiological evidence of tumor were not significantly different. Because PRL release is under tonic inhibitory dopaminergic control, the response to MIT reflects the degree of hypothalamic inhibitory activity. The data suggest that the significant hyperprolactinemia in OC subjects is under inhibitory control and that hypothalamic dopaminergic activity is increased in these subjects, in particular the subgroup with normal basal PRL levels. The impaired PRL response in subjects with pathological hyperprolactinemia indicates a loss of mediation of hypothalamic dopamine control over PRL release. The use of MIT provides a simple and reliable means of assessing central dopaminergic control of PRL release in hyperprolactinemic states. (J Clin Endocrinol Metab56: 692, 1983)