DOPAMINERGIC MODULATION OF TSH AND ITS SUBUNITS: IN VIVO AND IN VITRO STUDIES

We have studied the effects of dopamine on the secretion of TSH and its subunits in vivo and in vitro. Four normal controls, seven patients with primary hypothyroidism, two patients with peripheral resistance to thyroid hormone (PRTH), and two patients with α‐secreting pituitary tumours underwent a 3‐h dopamine infusion (4 μg/kg/min). Serial blood samples were drawn for TSH, PRL, α, and TSH‐β subunit. In normal subjects, TSH fell from 2·1 ± 0·9 (±SE) to 0·7 ± 0·1 μU/ml (P < 0·05), and α declined from 1·5 ± 0·4 to 1·0 ± 0·1 ng/ml (P < 0·01). TSH‐β was at or slightly above the detection limits of the assay before and after dopamine. In hypothyroidism, basal serum TSH was 81 ± 14 μ/ml. With dopamine, TSH fell to 35 ± 8 μU/ml (P < 0·001), while α decreased from 3·2 ± 0·4 to 2·0 ± 0·3 ng/ml (P < 0·001). Serum TSH‐β also declined from 0·97 ± 0·06 to 0·57 ± 0·05 ng/ml (P 0·001). A similar fall in TSH and α was seen in the two patients with PRTH. In normals and hypothyroid patients, the percentage change in α concentration was significantly less than that observed for intact TSH. This is due presumably to the contribution of the gonadotrophs to the circulating α pool. TSH and TSH‐β were undetectable in the two pituitary tumour patients, and α declined only slightly in each patient after dopamine. The in vitro effects of dopamine were studied using cultured bovine anterior pituitary cells. Dopamine (10⁻⁴‐10⁻⁸ mol/l) did not change basal TSH, α, or TSH‐β release. However, dopamine at all doses significantly blunted TRH (10⁻⁷ mol/l)‐stimulated TSH and TSH‐β release, and blunted TRH‐mediated α release at the two highest dopamine doses. These data suggest that dopamine modulates both TSH and TSH subunit secretion. These effects may be exerted directly at the level of the thyrotroph.