Differences between rats and mice in the leptin action on the paraventricular nucleus of the hypothalamus: Implications for the regulation of the hypothalamic-pituitary-thyroid axis
Differences between rats and mice in the leptin action on the paraventricular nucleus of the hypothalamus: Implications for the regulation of the hypothalamic-pituitary-thyroid axis
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DOI：
10.1111/jne.12895
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发表时间：
2020-08-24
影响因子：
3.2
通讯作者：
Donato, Jose, Jr.
中科院分区：
文献类型：
--
作者：
Campos, Ana M. P.;Teixeira, Pryscila D. S.;Donato, Jose, Jr.
以往的研究表明，瘦素通过直接和间接的机制调节下丘脑-垂体-甲状腺（HPT）轴。间接机制涉及瘦素作用于表达阿黑皮素原（POMC）和刺鼠相关肽（AgRP）的神经元。这些细胞支配下丘脑室旁核（PVH），在那里它们调节促垂体促甲状腺激素释放激素（TRH）产生神经元。其直接机制涉及PVH TRH神经元亚群中瘦素受体（LepR）的表达。然而，据我们所知，LepR在小鼠PVH TRH神经元中的存在尚未得到明确证实。因此，我们研究了大鼠和小鼠之间可能的种属特异性差异的机制招募瘦素调节HPT轴。我们观察到，急性瘦素注射诱导磷酸化的信号转导和转录激活因子3（pSTAT 3），瘦素反应细胞的标志物，在46.2 +/- 8.0%的PVH proTRH免疫反应神经元大鼠。相比之下，在小鼠PVH共表达瘦素诱导的pSTAT 3或LepR的proTRH阳性神经元的数量微不足道。同样，在大鼠中，中枢瘦素注射增加了含有cAMP反应元件结合蛋白磷酸化的PVH proTRH神经元的百分比，但在小鼠中没有。我们研究了PVH中AgRP和POMC轴突的神经支配，并观察到与小鼠相比，大鼠在PVH中表现出更密集的POMC神经支配，而大鼠和小鼠在PVH中表现出相似的AgRP轴突密度。总之，大鼠和小鼠在瘦素调节HPT轴的直接和间接机制中表现出重要的种属特异性差异。
Previous studies indicate that leptin regulates the hypothalamic-pituitary-thyroid (HPT) axis via direct and indirect mechanisms. The indirect mechanism involves leptin action in pro-opiomelanocortin (POMC)- and agouti-related peptide (AgRP)-expressing neurones. These cells innervate the paraventricular nucleus of the hypothalamus (PVH) where they modulate hypophysiotrophic thyrotrophin-releasing hormone (TRH)-producing neurones. The direct mechanism involves the expression of leptin receptor (LepR) in a subpopulation of PVH TRH neurones. However, to our knowledge, the existence of LepR in PVH TRH neurones of mice has not been clearly confirmed. Therefore, we investigated possible species-specific differences between rats and mice with respect to the mechanisms recruited by leptin to regulate the HPT axis. We observed that an acute leptin injection induced phosphorylated signal transducer and activator of transcription 3 (pSTAT3), a marker of leptin-responsive cells, in 46.2 +/- 8.0% of PVH proTRH immunoreactive neurones in rats. By contrast, an insignificant number of proTRH positive neurones in the mouse PVH co-expressed leptin-induced pSTAT3 or LepR. Similarly, central leptin injection increased the percentage of PVH proTRH neurones containing cAMP response element-binding protein phosphorylation in rats, but not in mice. We investigated the innervation of AgRP and POMC axons in the PVH and observed that rats exhibited a denser POMC innervation in the PVH compared to mice, whereas rats and mice showed similar density of AgRP axons in the PVH. In conclusion, rats and mice exhibit important species-specific differences in the direct and indirect mechanisms used by leptin to regulate the HPT axis.