title: Dexamethasone stimulates the expression of ghrelin and its receptor in rat hypothalamic 4B cells.
abstract: Growth hormone (GH)-releasing peptides (GHRPs) are synthetic peptides that strongly induce GH release. GHRPs act via a specific receptor, the GHRP receptor (GHSR), of which ghrelin is a natural ligand. GHRPs also induce adrenocorticotropic hormone (ACTH) release in healthy subjects. GHRPs or ghrelin stimulate ACTH release via corticotropin-releasing factor (CRF) and arginin vasopressin in the hypothalamus. Stress-activated CRF neurons are suppressed by glucocorticoids in the hypothalamic paraventricular nucleus (PVN), while CRF gene is up-regulated by glucocorticoids in the PVN cells without the influence of input neurons. However, little is known about the regulation of ghrelin and GHSR type 1a (GHSR1a) genes by glucocorticoids in PVN cells. To elucidate the regulation of ghrelin and GHSR gene expression by glucocorticoids in PVN cells, here we used a homologous PVN neuronal cell line, hypothalamic 4B, because these cells show characteristics of the parvocellular neurons of the PVN. These cells also express ghrelin and GHSR1a mRNA. Dexamethasone increased ghrelin mRNA levels. A potent glucocorticoid receptor antagonist, RU-486, significantly blocked dexamethasone-induced increases in ghrelin mRNA levels. Dexamethasone also significantly stimulated GHSR1a mRNA and protein levels. Finally, ghrelin increased CRF mRNA levels, as did dexamethasone. Incubation with both dexamethasone and ghrelin had an additive effect on CRF and ghrelin mRNA levels. The ghrelin-GHSR1a system is activated by glucocorticoids in the hypothalamic cells.
authors: Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan. kkageyama@hkg.odn.ne.jp
authors: Kazunori
authors: K
authors: Kageyama
authors: Kanako
authors: K
authors: Akimoto
authors: Satoshi
authors: S
authors: Yamagata
authors: Aya
authors: A
authors: Sugiyama
authors: Shingo
authors: S
authors: Murasawa
authors: Yutaka
authors: Y
authors: Watanuki
authors: Naoki
authors: N
authors: Tamasawa
authors: Toshihiro
authors: T
authors: Suda
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D054439:Ghrelin / Q000235:genetics* / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D054440:Receptors, Ghrelin / Q000235:genetics* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D054439:Ghrelin; D012333:RNA, Messenger; D054440:Receptors, Ghrelin; D003907:Dexamethasone