Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Mol Cell Endocrinol. 2011 Jul 20;341(1-2):71-7. doi: 10.1016/j.mce.2011.05.028. Epub 2011 Jun 1.
Mimecan is a protein of unknown function that is expressed in the pituitary tissues of mouse and human. In this study, we observed the function of mimecan on the proopiomelanocortin (POMC) gene in the pituitary and the hypothalamo-pituitary-adrenal axis (HPAA). Incubating pituitary corticotroph AtT-20 cells with recombinant mimecan protein stimulated adrenocorticotrophic hormone (ACTH) secretion without significantly up-regulating POMC gene expression. In addition, pituitary corticotroph AtT-20 cell corticotropin-releasing hormone receptor 1 (CRHR1) gene expression was induced by mimecan. Interestingly, long-term mimecan overexpression in corticotroph cells increased CRHR1 mRNA levels while slightly decreasing POMC mRNA expression and ACTH secretion. Using mimecan knockout mice, we found that, although the serum ACTH concentration was not significantly different between wild type and mimecan knockout mice under basal conditions, the serum ACTH level was relatively lower in mimecan knockout mice after treatment with corticotropin-releasing hormone (CRH). Meanwhile, we observed that POMC and CRHR1 gene expression decreased in primary cultured knockout mouse pituitary cells compared with wild type cells. Taken together, these data suggest that mimecan expressed in pituitary corticotroph cells mainly regulates ACTH secretion in the pituitary and coordinates the HPAA.
mimecan 是一种未知功能的蛋白，在人和鼠的垂体组织中表达。在本研究中，我们观察了 mimecan 对垂体前叶促肾上腺皮质激素（POMC）基因和下丘脑-垂体-肾上腺轴（HPAA）的作用。用重组 mimecan 蛋白孵育垂体促肾上腺皮质激素细胞 AtT-20，可刺激促肾上腺皮质激素（ACTH）分泌，而对 POMC 基因表达无明显上调作用。此外，mimcan 可诱导垂体促肾上腺皮质激素细胞促肾上腺皮质激素释放激素受体 1（CRHR1）基因表达。有趣的是，长期过表达 mimecan 可增加促肾上腺皮质激素细胞中的 CRHR1 mRNA 水平，而略降低 POMC mRNA 表达和 ACTH 分泌。使用 mimecan 基因敲除小鼠，我们发现，尽管在基础状态下野生型和 mimecan 基因敲除小鼠的血清 ACTH 浓度没有显著差异，但在给予促肾上腺皮质激素释放激素（CRH）后，mimecan 基因敲除小鼠的血清 ACTH 水平相对较低。同时，我们观察到与野生型细胞相比，初级培养的基因敲除小鼠垂体细胞中的 POMC 和 CRHR1 基因表达降低。综上所述，这些数据表明，垂体促肾上腺皮质激素细胞中表达的 mimecan 主要调节垂体中的 ACTH 分泌，并协调 HPAA。
