Dopaminergic Control of Thyrotropin, a-Subunit, Thyrotropin β-subunit, and Prolactin in Euthyroidism and Hypothyroidism: Dissociated Responses to Dopamine Receptor Blockade with Metoclopramide in Hypothyroid subjects*

Abstract

Thirteen female patients (ages 29-68 yr) with primary hypothyroidism and 10 euthyroid volunteers (5 females and 5 males, ages 22-43 yr) each received a single 10-mg dose of the dopamine-receptor blocking drug, metoclopramide. Intact TSH, PRL, α-subunit, and β-TSH responses over a 3-h period after drug administration have been compared with circulating hormone levels after placebo. In euthyroid subjects, intact TSH and a-subunit showed clear rises after metoclopramide compared with placebo (mean total incremental changes ± SE: intact TSH, 7.1 ± 1.3 vs. −3.4 ± 1.3 mU/liter. P < 0.001; a-subunit, 0.9 ± 0.2 us. −1.3 ± 0.6 ng/ml. P < 0.001). β-TSH changes, however, did not differ significantly from placebo (0.4 ± 0.5 vs. 1.1 ± 0.5 ng/ml, not significant). Total incremental responses (mean ± SE) were very much greater in hypothyroid than in euthyroid subjects for intact TSH (35.6 ± 9.8 vs. 7.1 ± 1.3 mU/liter, P < 0.001), a-subunit (7.2 ± 1.4 vs. 0.9 ± 0.2 ng/ml, P < 0.001), and β-TSH (6.5 ± 2.2 vs. 0.4 ± 0.5 ng/ ml, P< 0.001). Within the hypothyroid group the total incremental intact TSH responses (mean ± SE) were significantly less in patients with T₄ less than 50 nmol/liter than in patients with T₄ levels greater than 50 nmolliter (4.0 ± 7.7 vs. 52.5 ± 12.6 mU/liter, P < 0.02). In contrast, total incremental PRL, a-subunit, and β-TSH responses did not differ significantly between hypothyroid patients with T₄ less than 50 nmol/liter (PRL, 27.7 ± 8.0 mU/ liter; a-subunit, 8.5 ± 3.2 ng/ml; β-TSH, 3.2 ± 1.9 ng/ml) and those with T₄ levels greater than 50 nmol/liter (PRL, 45.2 ± 5.8 nU/liter; a-subunit, 6.4 ± 1.1 ng/nl; β-TSH, 8.5 ± 3.3 ng/ml). However, /8-TSH responses correlated directly with intact TSH responses in hypothyroid subjects (r = 0.63; P < 0.05), whereas PRL and a-subunit responses were not significantly related to the intact TSH response. Again in hypothyroid subjects, the PRL response was inversely related to subject age (r = −0.76; P < 0.05), whereas the intact TSH, a-subunit, and β-TSH responses were unrelated to subject age. We conclude from these data that, as with intact TSH, α-subunit and β-TSH release is under inhibitory dopaminergic control. Subunit release after dopamine antagonism is seen most clearly in hypothyroid subjects in whom the dominant negative feedback effects of thyroid hormones are reduced. The intact TSH response to dopamine antagonism and hence the dopami-nergic inhibition of intact TSH release declines with increasingly severe hypothyroidism. Intact TS H responses in hypothyroid subjects are paralleled by β-TSH responses, whereas PRL and a-subunit responses are not so clearly related to intact TSH responses and thyroid status.