Nesfatin-1, an 82 amino acid peptide cleaved from the N-terminal of its precursor nucleobindin-2 (NUCB2), is emerging as a multifunctional peptide in fish. The present study aimed to determine whether nesfatin-1 plays a role in fish somatic growth by modulating the growth hormone (GH)/insulin-like growth factor (IGF) axis, using a representative teleost model, the goldfish (Carassius auratus). The results demonstrated that a single i.p. injection of synthetic goldfish nesfatin-1 significantly decreased the expression of hypothalamic pacap (approximately 90%) and pituitary Gh (approximately 90%) mRNAs at 15 minutes post-injection. Serum GH levels were also reduced as a result of nesfatin-1 administration, by approximately 45% and 55% at 15 and 30 minutes post-injection, respectively. Likewise, in vitro treatment of goldfish dispersed pituitary cells with nesfatin-1 reduced Gh secretion, suggesting that nesfatin-1 acts directly on pituitary somatotrophs to inhibit Gh release. Exposure of cultured liver fragments to nesfatin-1 (0.1, 1 and 10 nmol L^-1) led to a significant reduction in igf-1 mRNA at 120 minutes and of igf-II mRNA at 30 and 60 minutes post-incubation. Collectively, these results indicate a suppressive role for nesfatin-1 on the goldfish GH/IGF axis. Immunohistochemical studies demonstrated that NUCB2/nesfatin-1-like immunoreactivity, although present in the goldfish pituitary, is not colocalised with GH in goldfish somatotrophs. Thus, nesfatin-1 does not appear to act in an autocrine manner to regulate GH secretion. Taken together, this research found that the pituitary gland is an important source of endogenous NUCB2/nesfatin-1 and also that nesfatin-1 directly suppresses the Gh/IGF axis in goldfish.

中文翻译：

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Nesfatin-1 是金鱼 (Carassius auratus) 生长激素-胰岛素样生长因子轴的抑制剂

Nesfatin-1 是一种 82 个氨基酸的肽，从其前体 nucleobindin-2 (NUCB2) 的 N 端切下，正在成为鱼类中的一种多功能肽。本研究旨在使用具有代表性的硬骨鱼模型金鱼 ( Carassius auratus ) ，通过调节生长激素 (GH)/胰岛素样生长因子 (IGF) 轴来确定 nesfatin-1 是否在鱼类体细胞生长中发挥作用。结果表明，单次腹腔注射合成金鱼 nesfatin-1 可显着降低下丘脑pacap（约 90%）和垂体Gh的表达（大约 90%）注射后 15 分钟的 mRNA。由于 nesfatin-1 给药，血清 GH 水平也分别在注射后 15 分钟和 30 分钟时降低了约 45% 和 55%。同样，用 nesfatin-1 对金鱼分散的垂体细胞进行体外处理会减少 Gh 的分泌，这表明 nesfatin-1 直接作用于垂体生长激素以抑制 Gh 的释放。将培养的肝脏片段暴露于 nesfatin-1（0.1、1 和 10 nmol L ^-1）导致120 分钟时igf-1 mRNA 和igf-II显着降低孵育后 30 和 60 分钟的 mRNA。总的来说，这些结果表明 nesfatin-1 对金鱼 GH/IGF 轴具有抑制作用。免疫组织化学研究表明，NUCB2/nesfatin-1 样免疫反应性虽然存在于金鱼垂体中，但在金鱼生长激素细胞中并未与 GH 共定位。因此，nesfatin-1 似乎不以自分泌方式调节 GH 分泌。综上所述，本研究发现垂体是内源性 NUCB2/nesfatin-1 的重要来源，而且 nesfatin-1 直接抑制金鱼的 Gh/IGF 轴。