ABSTRACT

Using chlorethylclonidine (CEC), an α_lb-adrenergic receptor-selective antagonist, we characterized α₁-adrenoceptor subtypes in rat thyroid gland, and investigated the effect of methimazole (MMI)-induced high TSH levels on α₁ receptor subtypes and noradrenaline-induced iodide organification. The density of thyroid α₁-adrenergic receptors was increased about sixfold in rats treated with MMI for 3 weeks compared with controls. Pretreatment of thyroid membrane preparations with CEC (10 μmol/l) caused an 83% decrease in specific 2-[β-(hydroxy-3-[¹²⁵I]iodophenyl) ethylaminomethyl]tetralone binding sites in MMI-treated rats, but only a 43% decrease in control rats. The density of CEC-insensitive α₁ receptors (α^1a) was similar in MMI-treated and control rats, so MMI was shown to increase CEC-sensitive α₁ receptors (α^1b).

Noradrenaline-stimulated iodide organification was threefold greater in MMI-treated rats than in control rats when values were expressed as a per cent increase over basal levels. Pretreatment of thyroid lobes with 10 μmol CEC/1 for 30 min caused a 66% decrease in maximal noradrenaline-induced iodide organification in MMI-treated rats, but a significantly lower decrease (49%) in control rats.

These results suggest that the rat thyroid gland contains both α_1a and α_1b receptors, both of which mediate noradrenaline-induced iodide organification, and also that TSH enhances noradrenaline-induced iodide organification by increasing α_1b receptor density.

Journal of Endocrinology (1990) 126, 317–322

ABSTRACT

We have characterized α₁-adrenergic receptor subtypes in functional rat thyroid cells, FRTL, with relation to iodide efflux, and have also examined the effect of TSH on α₁ receptor subtypes. FRTL cells grown in a medium containing 5 mU TSH/ml (6H cells) had five times the number of α₁ receptors of those maintained in TSH-free medium (5H cells) (11·2 fmol/10⁶ cells compared with 2·0 fmol/10⁶ cells). Pretreatment with chlorethylclonidine (CEC; 10 μmol/l), which inactivates only α_1b receptors, caused 98·8% and 97·0% decreases in the density of specific [³H]prazosin-binding sites in 5H and 6H cells respectively. LIGAND computer program analysis of the displacement curves for 2-(2,6-dimethoxyphenoxyethyl)-aminomethyl-1,4 benzodioxane (WB4101) showed that FRTL cells contained mostly low-affinity WB4101 sites. Using the phenoxybenzamine inactivation method, we found a linear relationship between α₁ receptor density and the cytosolic free Ca²⁺ concentration response in FRTL cells. Pre-exposure of intact FRTL cells to CEC caused a 98·7% decrease in noradrenaline-stimulated maximal increase in cytosolic free Ca²⁺. Also, CEC and 3,4,5-trimethoxybenzoic acid 8-(diethylamino) octyl ester (TMB-8), but not nicardipine, inhibited noradrenaline-stimulated iodine efflux. The results suggest that FRTL cells contain mostly the α_1b-adrenergic receptor subtype; that the α_1b receptors mediate cytosolic free Ca²⁺ and iodide efflux responses, and that TSH enhances these responses by increasing the α_1b receptor density without affecting the post-receptor mechanism.

Journal of Endocrinology (1990) 124, 433–441