Universidade de Sao Paulo, Instituto de Ciencias Biomedicas, Departamento de Fisiologia e Biofisica, Sao Paulo, Brazil.
Universidade de Sao Paulo, Instituto de Ciencias Biomedicas, Departamento de Anatomia, Sao Paulo, Brazil.
Neurosci Lett. 2021 May 1;752:135832. doi: 10.1016/j.neulet.2021.135832. Epub 2021 Mar 18.
During fasting or weight loss, the fall in leptin levels leads to suppression of thyrotropin-releasing hormone (TRH) expression in the paraventricular nucleus of the hypothalamus (PVH) and, consequently, inhibition of the hypothalamic-pituitary-thyroid (HPT) axis. However, differently than rats, just few PVH neurons express the leptin receptor in mice. In the present study, male adult rats and mice were submitted to 48 -h fasting to evaluate the consequences on proTRH peptide expression at the PVH level. Additionally, the proTRH peptide expression was also assessed in the brains of leptin-deficient (Lep) mice. We observed that approximately 50 % of PVH neurons of leptin-injected rats exhibited phosphorylation of the signal transducer and activator of transcription 3 (pSTAT3), a marker of leptin receptor activation. In contrast, very few PVH neurons of leptin-injected mice exhibited pSTAT3. Rats submitted to 48 -h fasting showed a significant reduction in the number of PVH immunoreactive neurons, as compared to fed rats. On the other hand, no changes in the number of PVH immunoreactive neurons were observed between fasted and fed mice. Next, the number of TRH immunoreactive cells was determined in the PVH, dorsomedial nucleus of the hypothalamus and nucleus raphe pallidus of Lep and wild-type mice and no significant differences were observed, despite reduced plasma T4 levels in Lep mice. Taken together, these findings provide additional evidence of the important species-specific differences in the mechanisms used by fasting and/or leptin to regulate the HPT axis.
在禁食或减肥期间，瘦素水平下降会导致下丘脑室旁核（PVH）中促甲状腺素释放激素（TRH）表达受到抑制，从而抑制下丘脑-垂体-甲状腺（HPT）轴。然而，与大鼠不同的是，在小鼠中只有少数 PVH 神经元表达瘦素受体。在本研究中，雄性成年大鼠和小鼠被禁食 48 小时，以评估其对 PVH 水平下 proTRH 肽表达的影响。此外，还评估了瘦素缺乏（Lep）小鼠大脑中的 proTRH 肽表达。我们观察到，大约 50%的瘦素注射大鼠的 PVH 神经元表现出信号转导和转录激活因子 3（pSTAT3）的磷酸化，这是瘦素受体激活的标志物。相比之下，瘦素注射小鼠的 PVH 神经元中很少有表现出 pSTAT3。与进食大鼠相比，禁食 48 小时的大鼠 PVH 免疫反应性神经元的数量显著减少。另一方面，禁食和进食小鼠之间的 PVH 免疫反应性神经元数量没有变化。接下来，在 Lep 和野生型小鼠的 PVH、下丘脑背内侧核和中缝苍白核中测定 TRH 免疫反应性细胞的数量，尽管 Lep 小鼠的血浆 T4 水平降低，但未观察到明显差异。综上所述，这些发现提供了更多的证据，表明禁食和/或瘦素调节 HPT 轴的机制在物种间存在重要的特异性差异。
