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Dopamine and L-dopa: inhibition of thyrotropin-stimulated thyroidal thyroxine release.

Abstract：

:Previous studies had suggested that norepinephrine (NE) and its precursors dopamine (DA) and L-DOPA acted similarly on iodine metabolism of isolated thyroid cells. Present studies indicate that this similarity extends to the inhibition by catecholamines of TSH-stimulated T4 release by mouse thyroids incubated in vitro. DA (5 X 10(-4) M), like NE, shown previously, inhibits TSH-stimulated T4 release. This inhibition was reversed by the alpha-blockers phentolamine, prazosin, and yohimbine, but not by the beta-blocker L-propranolol. DU-18288 and diethyldithiocarbamate, inhibitors of DA beta-hydroxylase, did not reduce DA inhibition, suggesting that prior conversion to NE was not a condition for DA activity. Apomorphine, a dopaminergic agonist but not a NE precursor, acted like DA, and its inhibition was also reversed by alpha-blockers. Furthermore, sulpiride, a dopaminergic blocker, reversed DA and apomorphine inhibition of TSH stimulation. These results suggest that DA inhibits TSH-stimulated T4 release through both adrenergic and dopaminergic receptors. On the other hand, L-DOPA, exerting an inhibition like that of DA, was also reversed by alpha-blockers, but its activity was greatly diminished by carbidopa, an inhibitor of aromatic L-amino acid decarboxylase, the enzyme converting L-DOPA to DA. This indicated that L-DOPA had to be converted to DA for activity. Both DA and L-DOPA inhibited stimulation of T4 release induced by (Bu)2cAMP, suggesting that their effect was exerted at a locus distal to cAMP generation. Indirect confirmation of a cAMP-independent pathway was obtained when DA inhibited TSH-stimulated cAMP formation, but, contrary to T4 release, this inhibition was not reversed by dopaminergic or adrenergic blockers. Presumably, therefore, DA inhibition of TSH-stimulated cAMP production was not related to T4 release. We conclude that 1) DA inhibits TSH-stimulated T4 release in mouse thyroids via alpha-adrenergic and dopaminergic receptors; 2) L-DOPA has to be converted to DA to produce inhibition; and 3) cAMP is unlikely to be an intermediary in DA inhibition.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Maayan ML,Sellitto RV,Volpert EM

doi

10.1210/endo-118-2-632

subject

Has Abstract

pub_date

1986-02-01 00:00:00

pages

632-6

issue

eissn

0013-7227

issn

1945-7170

journal_volume

118

pub_type

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Dopamine and L-dopa: inhibition of thyrotropin-stimulated thyroidal thyroxine release.