Polyamine regulation of the rat pro-opiomelanocortin gene expression in AtT-20 cells.
Polyamines are a ubiquitous group of amines that play diverse biological roles. In the anterior pituitary, intracellular polyamine levels are reported to show diurnal changes, although the biological significance remains to be elucidated. In this study, we examined the effects of polyamines on the transcriptional activity of the rat pro-opiomelanocortin (POMC) gene using AtT20PL, a clone of the AtT20 cell line in which an approximately 0.7 kb of the rat POMC 5' promoter-luciferase fusion gene was stably incorporated. The results showed that three representative polyamines (putrescine, spermidine and spermine) all stimulated POMC promoter activity in a time- and dose-related manner, spermine showing the most potent effect (maximum approximate three-fold increase). This effect was not observed under treatment with actinomycin D, suggesting the effect of polyamine at the transcriptional level. On the other hand, methylglyoxal bis (guanylhydrazone), an inhibitor of polyamine synthesis, showed the opposite effect, further supporting the positive role of intracellular polyamines. Taken together, our findings suggest that polyamines are involved in the regulation of POMC gene expression (especially in terms of diurnal changes) in corticotroph cells. The precise molecular mechanisms of polyamine effects await further research.
Yamamori
E
E
First Department of Internal Medicine, Nagoya University School of Medicine and Hospital, Nagoya, Japan.
Iwasaki
Y
Y
Aoki
Y
Y
Nomura
A
A
Tachikawa
K
K
Ariyoshi
Y
Y
Mutsuga
N
N
Morishita
M
M
Yoshida
M
M
Asai
M
M
Oiso
Y
Y
Saito
H
H
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D051379:Mice; D008935:Mitoguazone / Q000494:pharmacology; D011073:Polyamines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D011700:Putrescine / Q000494:pharmacology; D051381:Rats; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000819:agonists; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D011073:Polyamines; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface; C473605:extracellular calcium cation-sensing receptor, rat; D013096:Spermine; D011333:Pro-Opiomelanocortin; D008935:Mitoguazone; D013095:Spermidine; D011700:Putrescine