PMID- 33925368
OWN - NLM
STAT- MEDLINE
DCOM- 20210607
LR  - 20231111
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 9
DP  - 2021 Apr 27
TI  - Orexin A Enhances Pro-Opiomelanocortin Transcription Regulated by BMP-4 in Mouse 
      Corticotrope AtT20 Cells.
LID - 10.3390/ijms22094553 [doi]
LID - 4553
AB  - Orexin is expressed mainly in the hypothalamus and is known to activate the 
      hypothalamic-pituitary-adrenal (HPA) axis that is involved in various stress 
      responses and its resilience. However, the effects of orexin on the endocrine 
      function of pituitary corticotrope cells remain unclear. In this study, we 
      investigated the roles of orexin A in pro-opiomelanocortin (POMC) transcription 
      using mouse corticotrope AtT20 cells, focusing on the bone morphogenetic protein 
      (BMP) system expressed in the pituitary. Regarding the receptors for orexin, type 
      2 (OXR2) rather than type 1 (OX1R) receptor mRNA was predominantly expressed in 
      AtT20 cells. It was found that orexin A treatment enhanced POMC expression, 
      induced by corticotropin-releasing hormone (CRH) stimulation through upregulation 
      of CRH receptor type-1 (CRHR1). Orexin A had no direct effect on the POMC 
      transcription suppressed by BMP-4 treatment, whereas it suppressed Smad1/5/9 
      phosphorylation and Id-1 mRNA expression induced by BMP-4. It was further 
      revealed that orexin A had no significant effect on the expression levels of type 
      I and II BMP receptors but upregulated inhibitory Smad6/7 mRNA and protein levels 
      in AtT20 cells. The results demonstrated that orexin A upregulated CRHR signaling 
      and downregulated BMP-Smad signaling, leading to an enhancement of POMC 
      transcription by corticotrope cells.
FAU - Fujisawa, Satoshi
AU  - Fujisawa S
AD  - Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama 
      University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 
      2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan.
FAU - Komatsubara, Motoshi
AU  - Komatsubara M
AD  - Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama 
      University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 
      2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan.
FAU - Tsukamoto-Yamauchi, Naoko
AU  - Tsukamoto-Yamauchi N
AD  - Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama 
      University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 
      2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan.
FAU - Iwata, Nahoko
AU  - Iwata N
AD  - Department of General Medicine, Okayama University Graduate School of Medicine, 
      Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama 
      700-8558, Japan.
FAU - Nada, Takahiro
AU  - Nada T
AD  - Department of General Medicine, Okayama University Graduate School of Medicine, 
      Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama 
      700-8558, Japan.
FAU - Wada, Jun
AU  - Wada J
AD  - Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama 
      University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 
      2-5-1 Shikata-cho, Kitaku, Okayama 700-8558, Japan.
FAU - Otsuka, Fumio
AU  - Otsuka F
AUID- ORCID: 0000-0001-7014-9095
AD  - Department of General Medicine, Okayama University Graduate School of Medicine, 
      Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama 
      700-8558, Japan.
LA  - eng
GR  - 18K08479 and 19K17985/Ministry of Education, Culture, Sports, Science and 
      Technology/
GR  - 2018, 2019/Ofuji Endocrine Medical Award/
PT  - Journal Article
DEP - 20210427
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (Hcrt protein, mouse)
RN  - 0 (Orexins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Corticotropin-Releasing Hormone)
RN  - 5CLY6W2H1M (CRF receptor type 1)
RN  - 66796-54-1 (Pro-Opiomelanocortin)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
SB  - IM
MH  - Animals
MH  - Bone Morphogenetic Proteins/metabolism
MH  - Cell Line
MH  - Corticotrophs/metabolism
MH  - Corticotropin-Releasing Hormone/metabolism
MH  - Mice
MH  - Orexins/*metabolism/physiology
MH  - Phosphorylation
MH  - Pituitary Gland/metabolism
MH  - Pro-Opiomelanocortin/genetics/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptors, Corticotropin-Releasing Hormone/metabolism
MH  - Signal Transduction/drug effects
PMC - PMC8123825
OTO - NOTNLM
OT  - anterior pituitary
OT  - bone morphogenetic protein (BMP)
OT  - corticotrope
OT  - orexin
OT  - pro-opiomelanocortin (POMC)
COIS- The authors declare no conflict of interest.
EDAT- 2021/05/01 06:00
MHDA- 2021/06/08 06:00
PMCR- 2021/04/27
CRDT- 2021/04/30 01:31
PHST- 2021/03/15 00:00 [received]
PHST- 2021/04/24 00:00 [revised]
PHST- 2021/04/25 00:00 [accepted]
PHST- 2021/04/30 01:31 [entrez]
PHST- 2021/05/01 06:00 [pubmed]
PHST- 2021/06/08 06:00 [medline]
PHST- 2021/04/27 00:00 [pmc-release]
AID - ijms22094553 [pii]
AID - ijms-22-04553 [pii]
AID - 10.3390/ijms22094553 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Apr 27;22(9):4553. doi: 10.3390/ijms22094553.