title: Mimecan in pituitary corticotroph cells may regulate ACTH secretion and the HPAA.
abstract: 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.
authors.affiliation: 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.
authors.forename: Qin-Yun
authors.initials: QY
authors.lastname: Ma
authors.forename: Xiao-Na
authors.initials: XN
authors.lastname: Zhang
authors.forename: He
authors.initials: H
authors.lastname: Jiang
authors.forename: Zhi-Quan
authors.initials: ZQ
authors.lastname: Wang
authors.forename: Hui-Jie
authors.initials: HJ
authors.lastname: Zhang
authors.forename: Li-Qiong
authors.initials: LQ
authors.lastname: Xue
authors.forename: Ming-Dao
authors.initials: MD
authors.lastname: Chen
authors.forename: Huai-Dong
authors.initials: HD
authors.lastname: Song
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D052680:Corticotrophs / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D015870:Gene Expression; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010902:Pituitary Gland / Q000166:cytology*; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D061251:Primary Cell Culture; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D000099052:CRF Receptor, Type 1
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C512906:Ogn protein, mouse; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone