On the Role of the Central Noradrenergic and Dopaminergic Systems in the Regulation of TSH Secretion in the Rat

Abstract

Systemic administration of drugs affecting central noradrenergic and dopaminergic systems was used to evaluate their role in the regulation of TSH [thyrotropin] secretion in the rat. .alpha.-Methyl-p-tyrosine (.alpha.-MT) caused a depletion of brain norepinephrine and dopamine and a gradual decrease of serum TSH levels. Specific inhibitors of dopamine-.beta.-hydroxylase, diethyldithiocarbamate (DDC) and FLA 63 [disulfiram analog], depleted central norepinephrine only and led to a simultaneous striking decrease of serum TSH. Blockade of .alpha. adrenergic receptors with phenoxybenzamine, but not with phentolamine, also depressed serum TSH. Blockade of .beta. receptors with propranolol had no effect. In contrast, the centrally and peripherally acting .alpha. receptor agonist, clonidine, increased serum TSH, whereas the peripherally acting methoxamine caused a decrease, probably due to nonspecific stress effect. A dose-related rapid inhibition of TSH secretion was observed following stimulation of dopamine receptors with apomorphine. Injection of L-Dopa had a similar effect. Blockade of the dopamine receptors with pimozide did not alter serum TSH, while blockade with spiroperidol led to a slight increase. The cold-induced surge of TSH was abolished by pretreatment with DDC or phenoxybenzamine, reduced by apomorphine, but unaffected by pimozide or propranolol. The pituitary responsiveness to exogenous TRH [thyrotropin releasing hormone] was unaffected by administration of DDC or apomorphine. The central noradrenergic system may have a stimulatory effect on the release of TRH from the hypothalamus, reflected in the experiments by the changes of serum TSH levels. It probably provides the drive for the tonic release of TRH in resting conditions and stimuli for the enhanced secretion during cold exposure. The effect is probably mediated by a central .alpha.-adrenergic mechanism. Activation of the dopaminergic system is inhibitory, but the physiological role of this effect remains to be established.