Acute effect of thyroxine on pituitary neuromedin B content of hypothyroid rats and its correlation with TSH secretion.

Neuromedin B (NB) is a bombesin-like peptide that has been recently characterized as a physiological paracrine/autocrine inhibitor of thyrotropin (TSH) secretion. We report here the time course of the effect of thyroxine (T4) administration to hypothyroid rats on the anterior pituitary content of NB. Dutch-Miranda male rats weighing 250-300 g received 0.03% methimazole in the drinking water for 3 weeks. T4 (0.8 microgram/100 g body weight, sc) was given 1/2, 1, 3 or 6 h before sacrifice. One group received saline rather than T4 (hypothyroid control). The groups contained 6 to 8 animals each. NB, extracted from tissue by boiling in acetic acid, was measured by radioimmunoassay, using a highly specific antiserum. Pituitary NB content was significantly increased 4-fold, as early as 1/2 h after T4 injection, while serum TSH level was similar to that of the hypothyroid control group. The peak response to T4 was at 3 h after injection, when NB content was increased 8-fold (hypothyroid: 45 +/- 8; 1/2 h, 223 +/- 15; 1 h, 203 +/- 48; 3 h, 383 +/- 31; 6 h, 224 +/- 30 fmol/mg protein) and serum TSH decreased to the level of normal rats (0.93-1.5 ng/ml) generally observed in our laboratory (hypothyroid: 31 +/- 3; 1/2 h, 26 +/- 3; 1 h, 31 +/- 2; 3 h, 1.3 +/- 0.1; 6 h, 3.7 +/- 0.6 ng/ml). These data suggest that NB synthesis is rapidly induced by thyroxine and this might represent a new regulatory path involved in the acute inhibitory effect of thyroid hormones on TSH secretion.