Aging
Navigate
Research Paper|Volume 13, Issue 9|pp 13087—13107

The expression of mimecan in adrenal tissue plays a role in an organism’s responses to stress

Bin Su1, Qian-Yue Zhang2, Xue-Song Li3, Hui-Min Yu2, Ping Li2, Jun-Hua Ma2, Huang-Ming Cao2, Fei Sun2, Shuang-Xia Zhao2, Cui-Xia Zheng4, Ying Ru5,6, Huai-Dong Song2
  • 1Department of Blood Transfusion and Endocrinology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China
  • 2The Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostic and Endocrinology, Shanghai Ninth People’s Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao tong University School of Medicine, Shanghai 200011, China
  • 3Department of Endocrine Metabolism, Minhang Hospital, Fudan University, Shanghai 201199, China
  • 4Department of Respiration, Yangpu Hospital, Tongji University, Shanghai 200090, China
  • 5Department of Endocrinology and Metabolism, Anhui Provincial Hospital, The First Affiliated Hospital of University of Science and Technology of China, Hefei 230001, Anhui, China
  • 6Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
* Co-first authors
Received: January 19, 2021Accepted: April 2, 2021Published: May 10, 2021

Copyright: © 2021 Su et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Mimecan encodes a secretory protein that is secreted into the human serum as two mature proteins with molecular masses of 25 and 12 kDa. We found 12-kDa mimecan to be a novel satiety hormone mediated by the upregulation of the expression of interleukin (IL)-1β and IL-6 in the hypothalamus. Mimecan was found to be expressed in human pituitary corticotroph cells and was up-regulated by glucocorticoids, while the secretion of adrenocorticotropic hormone (ACTH) in pituitary corticotroph AtT-20 cells was induced by mimecan. However, the effects of mimecan in adrenal tissue on the hypothalamic–pituitary–adrenal (HPA) axis functions remain unknown. We demonstrated that the expression of mimecan in adrenal tissues is significantly downregulated by hypoglycemia and scalded stress. It was down-regulated by ACTH, but upregulated by glucocorticoids through in vivo and in vitro studies. We further found that 12-kDa mimecan fused protein increased the corticosterone secretion of adrenal cells in vivo and in vitro. Interestingly, compared to litter-mate mice, the diurnal rhythm of corticosterone secretion was disrupted under basal conditions, and the response to restraint stress was stronger in mimecan knockout mice. These findings suggest that mimecan stimulates corticosterone secretion in the adrenal tissues under basal conditions; however, the down-regulated expression of mimecan by increased ACTH secretion after stress in adrenal tissues might play a role in maintaining the homeostasis of an organism’s responses to stress.