title: Expression and regulation of neuromedin B in pituitary corticotrophs of male melanocortin 2 receptor-deficient mice.
abstract: The hypothalamic-pituitary-adrenal (HPA) axis is a major part of the neuroendocrine system that controls responses to stress, and has an important function in the regulation of various body processes. We previously created a mouse line deficient in the melanocortin 2 receptor (MC2R). MC2R-deficient mice (MC2R(-/-) mice) have high adrenocorticotropic hormone (ACTH) levels because of undetectable corticosterone levels. Increased neuromedin B (NMB) expression was recently reported in the pituitary gland of adrenalectomized mice, a model for acute adrenal insufficiency. To investigate gene expression in the pituitary gland under chronic adrenal deficiency, we examined the pituitary gland of MC2R(-/-) mice, a model of chronic adrenal insufficiency. To understand the molecular background of pituitary cells under chronic adrenal deficiency, we first performed DNA microarray analyses using the pituitary glands of the MC2R(-/-) mice. The DNA microarray analysis and real-time polymerase chain reaction showed that NMB expression was higher in the MC2R(-/-) than in the wild-type (WT) mice. We detected NMB expression in the MC2R(-/-) pituitary corticotrophs by immunohistochemistry using the specific antibodies for ACTH and NMB. In addition, the plasma NMB concentration was significantly higher in the MC2R(-/-) mice than in the WT mice. Subcutaneous implantation of a sustained-release corticosterone pellet decreased the expression of NMB mRNA as well as pituitary proopiomelanocortin mRNA. In isolated anterior pituitary cells, NMB mRNA expression was increased by the administration of corticotropin-releasing hormone (CRH) and was suppressed by dexamethasone treatment. In this study, we first demonstrate NMB expression in corticotrophs and its regulation by CRH and glucocorticoids. Furthermore, corticotrophs seemed to secrete NMB into the systemic circulation.
authors.affiliation: Division of Rheumatology, Endocrinology and Nephrology (H.K., H.M., A.N., T.K., T.A.), Hokkaido University Graduate School of Medicine, N 15, W 7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan; Division of Laboratory and Transfusion Medicine (C.S.), Hokkaido University Hospital, N 14, W 5, Kita-ku, Sapporo, Hokkaido 060-8648 Japan; Department of Diabetes and Endocrinology (S.N.), Sapporo Medical Center; NTT EC, S 1, W 15, Chuoh-Ku, Sapporo, Hokkaido 060-0061, Japan; and Faculty of Medicine (D.C.), Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan.
authors.forename: Hiraku
authors.initials: H
authors.lastname: Kameda
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyoshi
authors.forename: Chikara
authors.initials: C
authors.lastname: Shimizu
authors.forename: So
authors.initials: S
authors.lastname: Nagai
authors.forename: Akinobu
authors.initials: A
authors.lastname: Nakamura
authors.forename: Takuma
authors.initials: T
authors.lastname: Kondo
authors.forename: Dai
authors.initials: D
authors.lastname: Chida
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Atsumi
mesh_terms: D000309:Adrenal Insufficiency / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D052680:Corticotrophs / Q000187:drug effects / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010902:Pituitary Gland / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D044103:Receptor, Melanocortin, Type 2 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D005938:Glucocorticoids; D044103:Receptor, Melanocortin, Type 2; D011333:Pro-Opiomelanocortin; D003907:Dexamethasone; D015287:Neurokinin B; C038393:neuromedin B; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone