Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, China.
Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610065, China.
Genes (Basel). 2022 Sep 20;13(10):1680. doi: 10.3390/genes13101680.
Corticotropin (ACTH) is a pituitary hormone playing important roles in stress response within the hypothalamus-pituitary-adrenal (HPA) axis. The biosynthesis and secretion of ACTH are controlled by multiple factors, including corticotropin-releasing hormone (CRH). As a key hypothalamus-derived regulator, CRH binds to corticotropin-releasing hormone receptor 1 (CRHR1) in the anterior pituitary gland to regulate ACTH synthesis and release. Thus, CRH-binding protein (CRHBP), which binds CRH with high affinity to inhibit CRH-induced ACTH secretion from pituitary cells, draws wide attention. In contrast to the extensive investigation of CRHBP in mammals and other lower vertebrates, the gene structure, tissue expression and physiological functions of CRHBP in birds remain largely unknown. In the present study, using chicken (c-) as our animal model, we examined the gene structure, tissue expression and functionality of CRHBP. Our results showed that: (1) cDNA encodes a 345 amino acid precursor, which shares high sequence identity with that of mammals, reptiles, frogs and fish; (2) is abundantly expressed in the brain (cerebrum and hypothalamus), pituitary and ovary; (3) cCRHBP inhibits the signaling of cCRHRs induced by cCRH, thus reducing the cCRH-induced ACTH secretion from cultured chick pituitary cells; (4) stress mediators (e.g., glucocorticoids) and stress significantly upregulate mRNA expression in chickens, supporting its role as a negative feedback regulator in the HPA axis. The present study enriches our understanding of the conserved roles of CRHBP across vertebrates. In addition, chicken is an important poultry animal with multiple economic traits which are tightly controlled by the HPA axis. The characterization of the chicken gene helps to reveal the molecular basis of the chicken HPA axis and is thus beneficial to the poultry industry.
促肾上腺皮质激素（ACTH）是一种在下丘脑-垂体-肾上腺（HPA）轴内发挥重要作用的垂体激素。ACTH 的生物合成和分泌受多种因素控制，包括促肾上腺皮质激素释放激素（CRH）。作为一种关键的下丘脑衍生调节剂，CRH 与垂体前叶中的促肾上腺皮质激素释放激素受体 1（CRHR1）结合，调节 ACTH 的合成和释放。因此，CRH 结合蛋白（CRHBP），其与 CRH 以高亲和力结合，从而抑制 CRH 诱导的垂体细胞中 ACTH 的分泌，引起了广泛的关注。与对哺乳动物和其他低等脊椎动物中 CRHBP 的广泛研究相比，鸟类中 CRHBP 的基因结构、组织表达和生理功能仍知之甚少。在本研究中，我们使用鸡（c-）作为动物模型，研究了 CRHBP 的基因结构、组织表达和功能。我们的结果表明：（1）cDNA 编码一个 345 个氨基酸的前体，与哺乳动物、爬行动物、青蛙和鱼类具有高度的序列同一性；（2）在脑中（大脑和下丘脑）、垂体和卵巢中大量表达；（3）cCRHBP 抑制 cCRH 诱导的 cCRHRs 信号转导，从而减少培养的鸡垂体细胞中 cCRH 诱导的 ACTH 分泌；（4）应激调节剂（如糖皮质激素）和应激显著上调鸡中 的 mRNA 表达，支持其作为 HPA 轴负反馈调节剂的作用。本研究丰富了我们对 CRHBP 在脊椎动物中保守作用的认识。此外，鸡是一种重要的家禽动物，具有多种经济性状，这些性状由 HPA 轴紧密控制。鸡 基因的特征有助于揭示鸡 HPA 轴的分子基础，因此有利于家禽业。
