Analysis of pituitary gene expression of melanocortin 2 receptor deficient mice

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 72-87-HPA Axis
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-72
Hiraku Kameda*1, Osamu Nakagaki2, So Nagai3, Takuma Kondo4, Hideaki Miyoshi4, Tatsuya Atsumi4, Dai Chida5, Yoichiro Iwakura6 and Chikara Shimizu7
1Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan, 2Hokkaido University Graduate School of Medicine, Sapporo, Japan, 3Sapporo Medical Center NTT EC, Sapporo, Japan, 4Hokkaido University Graduate School of Medicine, 5Saitama Medical University, 6Tokyo University of Science, Tokyo, 7Hokkaido Univ Hosp, Sapporo, Japan
【Background and Aim】 Adrenocorticotropic hormone (ACTH) stimulates steroid synthesis in adrenal cortex. Since ACTH receptor (melanocortin 2 receptor : MC2R) is known to be expressed in not only the adrenal cortex but also other organs, actions of ACTH other than the steroid synthesis are assumed. The aim of this study is to investigate changes in pituitary gland at state of ACTH insufficiency using the MC2R deficient mice (MC2R-KO, Chida D, Shimizu C, et al. PNAS 2007) and a mouse pituitary cell line. 【Materials and Methods】 Microarray analysis: Using pituitary gland total RNA from five male MC2R-KO and five wild type (WT) mice of 18 week age, the change of gene expression was analyzed by DNA microarray method. The result was verified by the real-time PCR. Corticosterone administration: We carried out subcutaneous administration of corticosterone releasing pellets or placebo pellets to MC2R-KO and WT mice of 18-week age. Three week after pellet administration, total RNA of the pituitary gland was extracted, and gene expression was analyzed by the real-time PCR. Cell culture experiment: AtT-20/D16v-F2, which is a cell line of mouse pituitary carcinoma, was cultivated with or without corticotropin releasing hormone (CRH) or dexamethasone (DEX) to investigate the change of gene expression of proopiomelanocortin (POMC) and neuromedin B (NMB). 【Results】 In DNA microarray analysis, expression of neuromedin B mRNA in pituitaries of MC2R-KO mouse was 12.8 folds higher than that of WT, which was confirmed by realtime-PCR analysis. Subcutaneous administration of corticosterone releasing pellets suppressed both of POMC and NMB mRNA expression in pituitaries of MC2R-KO mouse. Neither CRH nor DEX alter NMB mRNA expression in AtT-20/D16v-F2 cell. 【Conclusion and Discussion】 Bombesin like peptides including NMB have relation to cell growth, energy metabolism, emotional action. It has been reported that NMB is a regulator of pituitary-thyroid axis function. In this study, the relationship between the hypothalamic-pituitary-adrenal (HPA) axis and NMB is suggested, although NMB was altered neither by CRH nor DEX in the corticotroph cell line. Further study to confirm the relationship between NMB and HPA axis is necessary.

Chida D, Nakagawa S, Nagai S, Sagara H, Katsumata H, Imaki T, Suzuki H, Mitani F, Ogishima T, Shimizu C, Kotaki H, Kakuta S, Sudo K, Koike T, Kubo M, Iwakura Y. Proc Natl Acad Sci USA.  Melanocortin 2 receptor is required for adrenal gland development, steroidogenesis, and neonatal gluconeogenesis. 2007 Nov 13;104(46):18205-10.

Nothing to Disclose: HK, ON, SN, TK, HM, TA, DC, YI, CS

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