2018年2月1日
Impaired processing of prohormones in secretogranin III-null mice causes maladaptation to an inadequate diet and stress
Endocrinology
- 巻
- 159
- 号
- 2
- 開始ページ
- 1213
- 終了ページ
- 1227
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1210/en.2017-00636
- 出版者・発行元
- Oxford University Press
Secretogranin III (SgIII), a member of the granin family, binds bothtoanother granin, chromogranin A (CgA), and to a cholesterol-rich membrane that is destined for secretory granules (SGs). The knock down of Sg III in adrenocorticotropic hormone (ACTH)-producingAtT-20cellslargelyimpairs the regulated secretion of CgA and ACTH. To clarify the physiological roles of SgIII in vivo, we analyzed hormone secretion and SG biogenesis in newly established SgIII-knockout (KO) mice. Although the SgIII-KO mice were viable and fertile and exhibited no overt abnormalities under ordinary rearing conditions, a high-fat/high-sucrose diet caused pronounced obesity in the mice. Furthermore, in the SgIII-KO mice compared with wild-type (WT) mice, the stimulated secretionofactive insulin decreased substantially, whereas the storage of proinsulin increased in the islets. The plasma ACTH was also less elevated in the SgIII-KO mice than in the WT mice after chronic restraint stress, whereas the storage level of the precursor proopiomelanocortin in the pituitary gland was somewhat increased. These findings suggest that the lack of SgIII causes maladaptation of endocrine cells to an inadequate diet and stress by impairing the proteolytic conversion of prohormones in SGs, whereas SG biogenesis and the basal secretion of peptide hormones under ordinary conditions are ensured by the compensatory upregulation of other residual granins or factors.
- リンク情報
- ID情報
-
- DOI : 10.1210/en.2017-00636
- ISSN : 1945-7170
- ISSN : 0013-7227
- PubMed ID : 29281094
- SCOPUS ID : 85042125745