PDF(Pubmed)
Abstract：
BACKGROUND: Energy allocation between growth and reproduction determines puberty onset and fertility. In mammals, peripheral hormones such as leptin, insulin and ghrelin signal metabolic information to the higher centres controlling gonadotrophin-releasing hormone neurone activity. However, these observations could not be confirmed in lower vertebrates, suggesting that other factors may mediate the energetic trade-off between growth and reproduction. A bioinformatic and experimental study suggested co-regulation of the circadian clock, reproductive axis and growth-regulating genes in zebrafish. While loss-of-function of most of the identified co-regulated genes had no effect or only had mild effects on reproduction, no such information existed about the co-regulated somatostatin, well-known for its actions on growth and metabolism.
RESULTS: We show that somatostatin signalling is pivotal in regulating fecundity and metabolism. Knock-out of zebrafish somatostatin 1.1 (sst1.1) and somatostatin 1.2 (sst1.2) caused a 20-30% increase in embryonic primordial germ cells, and sst1.2-/- adults laid 40% more eggs than their wild-type siblings. The sst1.1-/- and sst1.2-/- mutants had divergent metabolic phenotypes: the former had 25% more pancreatic α-cells, were hyperglycaemic and glucose intolerant, and had increased adipocyte mass; the latter had 25% more pancreatic β-cells, improved glucose clearance and reduced adipocyte mass.
CONCLUSIONS: We conclude that somatostatin signalling regulates energy metabolism and fecundity through anti-proliferative and modulatory actions on primordial germ cells, pancreatic insulin and glucagon cells and the hypothalamus. The ancient origin of the somatostatin system suggests it could act as a switch linking metabolism and reproduction across vertebrates. The results raise the possibility of applications in human and animal fertility.
RESULTS: We show that somatostatin signalling is pivotal in regulating fecundity and metabolism. Knock-out of zebrafish somatostatin 1.1 (sst1.1) and somatostatin 1.2 (sst1.2) caused a 20-30% increase in embryonic primordial germ cells, and sst1.2-/- adults laid 40% more eggs than their wild-type siblings. The sst1.1-/- and sst1.2-/- mutants had divergent metabolic phenotypes: the former had 25% more pancreatic α-cells, were hyperglycaemic and glucose intolerant, and had increased adipocyte mass; the latter had 25% more pancreatic β-cells, improved glucose clearance and reduced adipocyte mass.
CONCLUSIONS: We conclude that somatostatin signalling regulates energy metabolism and fecundity through anti-proliferative and modulatory actions on primordial germ cells, pancreatic insulin and glucagon cells and the hypothalamus. The ancient origin of the somatostatin system suggests it could act as a switch linking metabolism and reproduction across vertebrates. The results raise the possibility of applications in human and animal fertility.
摘要：
背景：生长和生殖之间的能量分配决定了青春期的开始和生育能力。在哺乳动物中,外周激素如瘦素，胰岛素和生长素释放肽向控制促性腺激素释放激素神经元活性的高级中心发出代谢信息。然而,这些观察结果无法在较低的脊椎动物中得到证实，这表明其他因素可能会调解增长和再生产之间的能量权衡。一项生物信息学和实验研究表明，生物钟可以共同调节，斑马鱼的生殖轴和生长调节基因。虽然大多数已确定的共调基因的功能丧失对生殖没有影响或仅有轻微影响，不存在关于共同调节的生长抑素的信息，以其对生长和新陈代谢的作用而闻名。
结果：我们表明生长抑素信号在调节繁殖力和代谢中至关重要。敲除斑马鱼生长抑素1.1（sst1.1）和生长抑素1.2（sst1.2）导致胚胎原始生殖细胞增加20-30％，sst1.2-/-成年人产卵比野生型兄弟姐妹多40％。sst1.1-/-和sst1.2-/-突变体具有不同的代谢表型：前者的胰腺α细胞多25％，是高血糖和葡萄糖不耐受，脂肪细胞量增加；后者的胰腺β细胞多25%，改善葡萄糖清除率和减少脂肪细胞质量。
结论：我们得出结论，生长抑素信号通过对原始生殖细胞的抗增殖和调节作用来调节能量代谢和繁殖力，胰腺胰岛素和胰高血糖素细胞和下丘脑。生长抑素系统的古老起源表明，它可以作为连接脊椎动物代谢和繁殖的开关。结果提高了在人类和动物生育中应用的可能性。
结果：我们表明生长抑素信号在调节繁殖力和代谢中至关重要。敲除斑马鱼生长抑素1.1（sst1.1）和生长抑素1.2（sst1.2）导致胚胎原始生殖细胞增加20-30％，sst1.2-/-成年人产卵比野生型兄弟姐妹多40％。sst1.1-/-和sst1.2-/-突变体具有不同的代谢表型：前者的胰腺α细胞多25％，是高血糖和葡萄糖不耐受，脂肪细胞量增加；后者的胰腺β细胞多25%，改善葡萄糖清除率和减少脂肪细胞质量。
结论：我们得出结论，生长抑素信号通过对原始生殖细胞的抗增殖和调节作用来调节能量代谢和繁殖力，胰腺胰岛素和胰高血糖素细胞和下丘脑。生长抑素系统的古老起源表明，它可以作为连接脊椎动物代谢和繁殖的开关。结果提高了在人类和动物生育中应用的可能性。
