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Mutual Effects of Orexin and Bone Morphogenetic Proteins on Gonadotropin Expression by Mouse Gonadotrope Cells
- Source :
- International Journal of Molecular Sciences; Volume 23; Issue 17; Pages: 9782
- Publication Year :
- 2022
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2022.
-
Abstract
- Orexin plays a key role in the regulation of sleep and wakefulness and in feeding behavior in the central nervous system, but its receptors are expressed in various peripheral tissues including endocrine tissues. In the present study, we elucidated the effects of orexin on pituitary gonadotropin regulation by focusing on the functional involvement of bone morphogenetic proteins (BMPs) and clock genes using mouse gonadotrope LβT2 cells that express orexin type 1 (OX1R) and type 2 (OX2R) receptors. Treatments with orexin A enhanced LHβ and FSHβ mRNA expression in a dose-dependent manner in the absence of GnRH, whereas orexin A in turn suppressed GnRH-induced gonadotropin expression in LβT2 cells. Orexin A downregulated GnRH receptor expression, while GnRH enhanced OX1R and OX2R mRNA expression. Treatments with orexin A as well as GnRH increased the mRNA levels of Bmal1 and Clock, which are oscillational regulators for gonadotropin expression. Of note, treatments with BMP-6 and -15 enhanced OX1R and OX2R mRNA expression with upregulation of clock gene expression. On the other hand, orexin A enhanced BMP receptor signaling of Smad1/5/9 phosphorylation through upregulation of ALK-2/BMPRII among the BMP receptors expressed in LβT2 cells. Collectively, the results indicate that orexin regulates gonadotropin expression via clock gene expression by mutually interacting with GnRH action and the pituitary BMP system in gonadotrope cells.
- Subjects :
- Orexins
bone morphogenetic protein (BMP)
clock
gonadotropin
orexin
pituitary
Organic Chemistry
Luteinizing Hormone, beta Subunit
General Medicine
Catalysis
Computer Science Applications
Gonadotropin-Releasing Hormone
Inorganic Chemistry
Mice
Pituitary Gland
Bone Morphogenetic Proteins
Follicle Stimulating Hormone, beta Subunit
Animals
RNA, Messenger
Physical and Theoretical Chemistry
Molecular Biology
Gonadotropins
Spectroscopy
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences; Volume 23; Issue 17; Pages
- Accession number :
- edsair.doi.dedup.....6edfd8c396b9778c6bd918dce2f1f1a1
- Full Text :
- https://doi.org/10.3390/ijms23179782