Impaired serum thyrotropin response to hypothyroidism in mice with disruption of neuromedin B receptor.
Neuromedin B (NB), a neuropeptide highly concentrated in pituitary, has been proposed to be an inhibitor of thyrotropin (TSH) secretion. Previous study showed that mice with disruption of neuromedin B receptor (NBR-KO) have higher TSH release in response to thyrotropin-releasing hormone (TRH), although TSH seems to have decreased bioactivity. Here we examined in NBR-KO mice the response of TSH to thyroid hormone (TH) deprivation, obtained by methimazole treatment, or excess, obtained by acute and chronic TH administration. In response to hypothyroidism NBR-KO mice exhibited a lower magnitude increase in serum TSH compared to wild-type (WT) mice (1.7 vs. 3.3-times increase compared to euthyroid values, respectively, P<0.001). One hour after a single T4 injection (0.4 microg/100 g BW), WT and NBR-KO hypothyroid mice presented similar degree of serum TSH reduction (54%, P<0.05). However, 3 h after T4 administration, WT mice presented serum TSH similar to hypothyroid baseline, while NBR-KO mice still had decreased serum TSH (30% reduced in comparison to hypothyroid baseline P<0.05). T3 treatment of euthyroid mice for 21 days, with progressively increasing doses, significantly reduced serum TSH similarly in WT and NBR-KO mice. Also, serum T4 exhibited the same degree of suppression in WT and NBR-KO. In conclusion, disruption of neuromedin B receptor did not interfere with the sensitivity of thyroid hormone-mediated suppression of TSH release, but impaired the ability of thyrotroph to increase serum TSH in hypothyroidism, which highlights the importance of NB in modulating the set point of the hypothalamus-pituitary-thyroid axis at hypothyroidism.
Oliveira
Karen J
KJ
Laboratório de Endocrinologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21949-900, Brazil.
Cabanelas
Adriana
A
Veiga
Marco Aurélio Lc
MA
Paula
Gabriela Sm
GS
Ortiga-Carvalho
Tânia M
TM
Wada
Etsuko
E
Wada
Keiji
K
Pazos-Moura
Carmen C
CC
D000818:Animals; D007037:Hypothyroidism / Q000097:blood* / Q000139:chemically induced; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018004:Receptors, Bombesin / Q000235:genetics / Q000502:physiology*; D013972:Thyrotropin / Q000097:blood* / Q000378:metabolism
D018004:Receptors, Bombesin; D013972:Thyrotropin