Neuromedin B (NB) and gastrin-releasing peptide (GRP) are mammalian bombesin-like peptides. Both peptides have inhibitory effects on thyrotropin (TSH) secretion, however NB is the one that proved to be physiologically relevant. The administration of NB reduces serum TSH of eu- and hypothyroid rats, while the antiserum against NB, that blocks the endogenous peptide, increases TSH secretion. NB is abundantly produced in thyrotrophs and acts locally as a autocrine factor to inhibit TSH release since isolated pituitaries increase the release of TSH in the presence of the specific antiserum. Thyroid hormones (TH) up-regulate pituitary NB peptide and mRNA content. This is a rapid effect: in hypothyroid rats it is seen within a few hours after a single injection of TH, and coincides with TSH suppression. These results suggest that NB could be an intermediary factor in the acute suppressive effect of TH on TSH secretion. TRH also rapidly changes NB expression. In normal rats, 15 to 30 minutes after TRH administration the pituitary NB peptide and mRNA content are already decreased. In experimental fasting and diabetes mellitus, which are characterized by inappropriately normal or decreased serum TSH, both the NB peptide and its mRNA pituitary content are increased. Octreotide, a somatostatin analog, also is able to increase pituitary neuromedin B content. Therefore, we propose that neuromedin B is a physiologically relevant local inhibitor of TSH secretion that may act as a final common pathway for hormones and neurohormones that modulate the rate of TSH secretion.
Thyrotrophin; Neuromedin B; Bombesin; Thyroid hormones; Autocrine regulation
