Domperidone directly stimulates TSH secretion in vitro

Abstract

Administration of the dopamine antagonist, domperidone [ 1,2] stimulates TSH secretion in man [3]. Since dopamine suppresses both in vivo and in vitro basal and stimulated TSH secretion [4-81 and there is evidence that dopamine and domperidone do not cross the blood-brain barrier [ 1,2,9], this stimulatory effect of domperidone has been attributed to antagonism of dopaminergic inhibition of anterior pituitary TSH secretion [ 31. As yet, however, a direct effect of domperidone on the thyrotroph has not been discounted. Here, we demonstrate a direct stimulatory effect of domperidone on basal TSH secretion from rat anterior pituitary cells in culture, in the absence of dopamine. Dopamine alone did not modify basal TSH secretion, but did antagonise the TSH stimulatory effect of domperidone. In contrast, domperidone had no effect on basal prolactin secretion, but did antagonise dopaminergic inhibition of prolaction secretion. These results suggest a differential sensitivity of lactotrophs and thyrotrophs to dopamine inhibition, and indicate that the in vivo TSH stimulatory effect of domperidone may not be entirely due to any dopaminergic antagonist properties of the drug.