Paradoxical effect of neuromedin B and thyroxin on thyrotropin secretion from isolated hyperthyroid pituitaries

Neuromedin B (NB) is a bombesin-like peptide that we recently characterized as a physiological autocrine inhibitor of thyrotropin (TSH) secretion. We now report the effect of NB, thyroxin (T4) and NB + thyroxin on basal and THR (50 nM)-stimulated TSH release from isolated hemipituitaries of hyperthyroid rats. To induce hyperthyroidism, 20 rats were treated with 0.03% methimazole for one month and then received T4, 4 micrograms/100 g body weight, sc, daily for 7 days. Each experimental group consisted of 7 to 9 hemipituitaries. TSH was measured using a rat TSH kit provided by NIDDK. Basal TSH release was paradoxically increased in the presence of 0.1 microM T4 or 0.1 microM NB and even two times higher in the presence of both (Control: 30.0 +/- 4.2 ng/ml; T4: 58.6 +/- 5.6 ng/ml; NB: 53.4 +/- 6.1 ng/ml; T4 + NB: 90.4 +/- 8.5 ng/ml). The percent increment above basal TSH levels after TRH was higher only in the presence of NB (Control: 44.5 +/- 8.2%, NB: 105.3 +/- 18.8%; P < 0.05). Altered responsiveness in hyperthyroidism and direct modification of the intracellular metabolism of T4 are mechanisms that could explain this paradoxical effect.