Dopaminergic modulation of TSH and its subunits: in vivo and in vitro studies.

Abstract

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 alpha-secreting pituitary tumours underwent a 3-h dopamine infusion (4 micrograms/kg/min). Serial blood samples were drawn for TSH, PRL, alpha, and TSH-beta subunit. In normal subjects, TSH fell from 2.1 +/- 0.9 (+/- SE) to 0.7 +/- 0.1 microU/ml (P less than 0.05), and alpha declined from 1.5 +/- 0.4 to 1.0 +/- 0.1 ng/ml (P less than 0.01). TSH-beta was at or slightly above the detection limits of the assay before and after dopamine. In hypothyroidism, basal serum TSH was 81 +/- 14 microU/ml. With dopamine, TSH fell to 35 +/- 8 microU/ml (P less than 0.001), while alpha decreased from 3.2 +/- 0.4 to 2.0 +/- 0.3 ng/ml (P less than 0.01). Serum TSH-beta also declined from 0.97 +/- 0.06 to 0.57 +/- 0.05 ng/ml (P less than 0.001). A similar fall in TSH and alpha was seen in the two patients with PRTH. In normals and hypothyroid patients, the percentage change in alpha concentration was significantly less than that observed for intact TSH. This is due presumably to the contribution of the gonadotrophs to the circulating alpha pool. TSH and TSH-beta were undetectable in the two pituitary tumour patients, and alpha 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, alpha, or TSH-beta release. However, dopamine at all doses significantly blunted TRH (10(-7) mol/l)-stimulated TSH and TSH-beta release, and blunted TRH-mediated alpha 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.