Dopamine Is a Physiological Regulator of Thyrotrophin (Tsh) Secretion in Normal Man

Abstract

Using a sensitive and precise radioimmunoassay for human TSH we have demonstrated significant elevations in serum TSH levels in euthyroid volunteers following administration of the dopamine receptor blocking drug metoclopramide when compared with placebo. The degree of TSH response is significantly greater in females than in males and is sustained over a 3-hour period after a single oral 10 mg dose of metoclopramide. The degree of TSH release after metoclopramide is inversely related to the basal TSH level suggesting that dopamine is a determinant of low daytime TSH levels and is thus implicated in the circadian rhythm of TSH secretion. Pretreatment with 10 mg of metoclopramide orally, one hour before TRH administration leads to significant enhancement of the TSH response to TRH. Our findings provide further evidence for the physiological inhibitory role of dopamine in the contol of TSH secretion in normal man. The possible mode of action of dopamine and the clinical implications of this neuroregulatory pathway are discussed.

Neurotransmitter Control of Thyrotropin Secretion

“…Sowers et al [122] were probably the first to describe a slight elevation of serum TSH levels in euthyroid men following administration of metoclopramide. Their re sults were subsequently confirmed and expanded by other workers using metoclopramide [41,109,110], the related drug sulpiride [68,143] or the novel blocker, domperidone [20,67,94]. It soon became evident that the magnitude of the rise in the TSH levels is determined by several factors.…”

“…Women in general show a larger response than men, who on occasion do not react at all [6. 51, 68,109]. Another factor is the thyroid status.…”

Modulation of the actions of tyrosine by α2‐adrenoceptor blockade

“…The mechanism of the stimulant effect of tyrosine on these two hormones is unknown, but it is possible that tyrosine or one of its derivatives may stimulate the secretion of the thyrotrophin releasing hormone (TRH) or inhibit or antagonize the action of hypothalamic dopamine, which would result in an increase in prolactin and TSH secretion. The apparently more potent action of tyrosine in stimulating prolactin than TSH secretion is compatible with dopaminergic inhibition or antagonism, as dopamine antagonists have a greater effect on prolactin than TSH secretion in man (Scanlon et al, 1979). Interestingly, serum prolactin concentrations began to fall while plasma tyrosine concentrations were still high.…”

Influence of dopamine receptor agonists on gastric acid secretion induced by intraventricular administration of thyrotropin‐releasing hormone in the perfused stomach of anaesthetized rats

“…TRH-induced release of growth hormone was suppressed after dopaminergic stimuli, such as bromocriptine therapy (Jackson, 1980). Dopamine has inhibitory effects on the TSH secretion induced by TRH in the thyrotrope (Scanlon, Weightman, Shale, Mora, Heath, Snow, Lewis & Hall, 1979). Further evidence for the dopaminergic inhibition of the TRH-TSH secretion was obtained in rats (Mannisto, Nattila & Kaakkola, 1981).…”