Mar, 2019
Orexin A modulates prolactin production by regulating BMP-4 activity in rat pituitary lactotorope cells.
Peptides
- ,
- ,
- ,
- ,
- ,
- ,
- ,
- Volume
- 113
- Number
- First page
- 35
- Last page
- 40
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1016/j.peptides.2019.01.002
- Publisher
- ELSEVIER SCIENCE INC
The impact of orexins on anterior pituitary function has yet to be clarified. We studied the effects of orexin A and its interaction with the bone morphogenetic protein (BMP) system on the regulatory role of prolactin synthesis using rat lactotrope GH3 cells expressing BMP-4. Orexin type 1 receptor (OX1R), but not type 2 receptor (OX2R), was predominantly expressed in GH3 cells. Orexin A suppressed forskolin-induced, but not basal, prolactin mRNA expression without reducing cAMP levels. Of note, orexin A suppressed BMP-4-induced prolactin mRNA and cAMP synthesis. Impairment of the effects of orexin by chemical inhibitors suggested involvement of the P38 pathway in the OX1R activity that suppresses BMP-4-induced PRL expression. Given that inhibition of BMP-receptor signaling reduced prolactin mRNA levels, endogenous BMP action is likely to be linked to the activation of prolactin synthesis by GH3 cells. Orexin A was revealed to suppress Smad1/5/9 phosphorylation and Id-1 transcription induced by BMP-4, which was restored in the presence of orexin-receptor antagonists, suggesting that the inhibitory effect of orexin A occurred via OX1R. Orexin A also reduced ALK-3 expression but increased inhibitory Smad6/7 expression, while BMP-4 treatment downregulated OX1R expression. These results indicated that orexin A plays an inhibitory role in prolactin production through suppression of endogenous BMP activity in GH3 cells, suggesting that a new functional role of the interaction between orexin and BMP-4 is modulation of prolactin levels in lactotrope cells.
- Link information
- ID information
-
- DOI : 10.1016/j.peptides.2019.01.002
- ISSN : 0196-9781
- eISSN : 1873-5169
- Pubmed ID : 30721716
- Web of Science ID : WOS:000459508600004