Lipopolysaccharide stimulates proopiomelanocortin gene expression in AtT20 corticotroph cells.
While lipopolysaccharides (LPS) are known to activate the hypothalamo-pituitary-adrenal axis, their direct effects on proopiomelanocortin (POMC) and adrenocorticotropin (ACTH) expression at the pituitary level through Toll-like receptors (TLRs) remain unclear. In this study, we examined the effects of LPS on ACTH secretion and the transcription of the POMC gene in the AtT20 mouse pituitary corticotroph cell line. RT-PCR analysis showed that TLR1-4 and 6 subtype mRNAs were expressed in AtT20 cells. When the cells were treated with LPS, a significant increase in the 5'-promoter activity of POMC gene was observed at 24 h, without any stimulatory effect on ACTH secretion. LPS also stimulated the expression of c-Fos gene and protein, and AP1-, but not NF-kappaB-, mediated transcription. Overall, our data show the expression of TLRs in the pituitary corticotroph cells, and suggest the direct stimulatory effect of LPS on POMC gene expression via TLR (probably TLR4), although the intracellular signaling pathways in the corticotroph may be different from those in immune cells.
Iwasaki
Yasumasa
Y
Department of Endocrinology, Metabolism, and Nephrology, Kochi Medical School, Kochi University, Nankoku, Japan.
Taguchi
Takafumi
T
Nishiyama
Mitsuru
M
Asai
Masato
M
Yoshida
Masanori
M
Kambayashi
Machiko
M
Takao
Toshihiro
T
Hashimoto
Kozo
K
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D052680:Corticotrophs / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000235:genetics* / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
D008070:Lipopolysaccharides; D016328:NF-kappa B; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D018808:Transcription Factor AP-1; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone