Role of neuromedin B in the in vitro thyrotropin release in response to thyrotropin-releasing hormone from anterior pituitaries of eu-, hypo-, and hyperthyroid rats.
A role of neuromedin B (NB), a bombesin-like peptide, as an inhibitory paracrine/autocrine regulator of thyrotropin secretion has been suggested. We previously reported (10) that basal thyroid-stimulating hormone (TSH) release in vitro was decreased by NB and increased in the presence of a highly potent antiserum against NB (aNB). In these experiments, we studied the effects of NB (10(-11) - 10(-7) M) and antiserum against NB (aNB, 1:2000 dilution) on basal TSH release and the response to thyrotropin-releasing hormone (TRH) (0.5 x 10(-8) M) from incubated anterior pituitaries from eu-, hypo-, and hyperthyroid rats. As expected, in euthyroid rats NB decreased basal and TRH-stimulated TSH release, but only at the highest concentration tested (10(-7) M). Incubation of the pituitaries from euthyroid rats with the antiserum against NB increased basal TSH release above that from glands of normal rabbit serum-incubated controls, as anticipated based on the concept that NB inhibits TSH release from the pituitary glands of euthyroid animals. The antiserum did not augment the response to TRH, suggesting that NB released in this situation, although suppressing basal release, had no effort on the stimulated release induced by TRH. Glands from hypothyroid rats had a slightly lower basal TSH release and decreased response to TRH than glands from euthyroid rats. They responded with a decrease in basal TSH release at a much lower concentration of NB (10(-9) M) than pituitaries from euthyroid animals. Surprisingly, pituitaries from hypothyroid rats showed a paradoxical increased release of TSH in response to the lowest concentration of NB (10(-11) M), which decreased with increasing concentrations and was not distinguishable from control release in the presence of TRH at the highest concentration of NB (10(-7) M). We hypothesize that the increased responsiveness to the inhibition of basal TSH release by NB in the hypothyroid pituitaries may be related to an upregulation of NB receptors in this situation, in which the release of NB is diminished because of loss of feedback via thyroid hormones. The view that NB secretion was reduced in the hypothyroid situation was supported by the fact that there was no change in TSH release or the response to TRH following treatment with aNB in these animals. Remarkably, in the glands from the hyperthyroid rats, although basal TSH secretion was significantly lower than that from euthyroid pituitaries and response to TRH was also decreased, NB (10(-11)-10(-7) M) instead of decreasing TSH release augmented it significantly. Also, the response to TRH was significantly augmented but only at the lowest concentration of NB tested (10(-11 M). That NB was probably being secreted in vitro from the hyperthyroid pituitaries was indicated by an increased basal TSH release as well as a higher TSH medium concentration after TRH in the presence of the aNB. These results support the concept that the glands from the hyperthyroid animals secrete more NB because of positive feedback of thyroid hormones directly on the thyrotropes to increase NB synthesis and release which downregulates NB receptors on the gland. This downregulation of receptors in some manner reverses the inhibitory action of NB on basal and TRH-stimulated TSH release. In conclusion, the results provide further evidence for an important role of NB as an autocrine regulator of TSH release, which is modulated by increased release of NB induced by thyroid hormones.
Pazos-Moura
C C
CC
Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Brasil.
Moura
E G
EG
Rettori
V
V
Polak
J
J
McCann
S M
SM
D000818:Animals; D006980:Hyperthyroidism / Q000503:physiopathology*; D007037:Hypothyroidism / Q000503:physiopathology*; D007106:Immune Sera / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000276:immunology / Q000502:physiology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D007106:Immune Sera; D013973:Thyrotropin-Releasing Hormone; D015287:Neurokinin B; C038393:neuromedin B; D013972:Thyrotropin