TY - JOUR
T1 - Orexin a enhances pro-opiomelanocortin transcription regulated by bmp-4 in mouse corticotrope att20 cells
AU - Fujisawa, Satoshi
AU - Komatsubara, Motoshi
AU - Tsukamoto-Yamauchi, Naoko
AU - Iwata, Nahoko
AU - Nada, Takahiro
AU - Wada, Jun
AU - Otsuka, Fumio
N1 - Funding Information:
Funding: The present work was supported by Grants-in-Aid for Scientific Research (No.18K08479, 19K17985 and 21K08556) and Ofuji Endocrine Medical Award.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/5/1
Y1 - 2021/5/1
N2 - 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 upregu-lation 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.
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 upregu-lation 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.
KW - Anterior pituitary
KW - Bone morphogenetic protein (BMP)
KW - Corticotrope
KW - Orexin
KW - Pro-opiomelanocortin (POMC)
UR - http://www.scopus.com/inward/record.url?scp=85104734574&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85104734574&partnerID=8YFLogxK
U2 - 10.3390/ijms22094553
DO - 10.3390/ijms22094553
M3 - Article
C2 - 33925368
AN - SCOPUS:85104734574
SN - 1661-6596
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 9
M1 - 4553
ER -