Liu Lulu, Yang Shilong, Chai Longhui, Zhang Shipei, Liu Dan, Xu Haitao, Zhao Yue, Chen Shiyu, Jiang Guangshun, Li Bin
College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin, China.
College of Wildlife and Protected Area, Northeast Forestry University, Harbin, China.
Commun Biol. 2025 Mar 31;8(1):526. doi: 10.1038/s42003-025-07980-6.
The Felidae exhibits remarkable diversity in body size, with lengths ranging from 50 to 370 cm and weights from 1.1 to 423 kg. However, the underlying mechanisms driving this variation remain poorly understood. Here, we focused on the Siberian tiger (Panthera tigris altaica), the largest of the six extant tiger subspecies, and revealed the surprising expression of nicotinic acetylcholine receptors (nAChRs) in pituitary somatotrophs, which are crucial for regulating growth hormone (GH) secretion. Single-nucleus RNA sequencing of Siberian tiger pituitary cells exhibited the coexpression of CHRNA3, CHRNB4, and CHRNA5 genes in somatotrophs, a finding confirmed by electrophysiological experiments demonstrating the formation of functional nAChRs. Activation of these receptors elevated intracellular Ca levels, thereby enhancing GH secretion in somatotrophs. Notably, nAChRs were absent in the pituitary glands of mice, domestic cats, and rats, both in early life and adulthood, despite high acetylcholine levels during early life. These results suggest that nAChRs in Siberian tiger somatotrophs play a pivotal role in GH release, offering new insights into the molecular mechanisms regulating body size in these terrestrial giants.
猫科动物在体型上表现出显著的多样性，体长从50厘米到370厘米不等，体重从1.1千克到423千克。然而，驱动这种变异的潜在机制仍知之甚少。在这里，我们聚焦于东北虎（Panthera tigris altaica），它是现存六个老虎亚种中体型最大的，并且揭示了烟碱型乙酰胆碱受体（nAChRs）在垂体生长激素细胞中令人惊讶的表达，这些细胞对于调节生长激素（GH）的分泌至关重要。对东北虎垂体细胞进行的单核RNA测序显示，生长激素细胞中CHRNA3、CHRNB4和CHRNA5基因共表达，这一发现通过电生理实验得到证实，该实验证明了功能性nAChRs的形成。这些受体的激活提高了细胞内钙离子水平，从而增强了生长激素细胞中GH的分泌。值得注意的是，在小鼠、家猫和大鼠的垂体中，无论是在幼年还是成年期，尽管幼年时乙酰胆碱水平较高，但都不存在nAChRs。这些结果表明，东北虎生长激素细胞中的nAChRs在GH释放中起关键作用，为这些陆地巨兽体型调节的分子机制提供了新的见解。
