Evidence from studies with N-ethyl-maleimide and 12-O-tetradecanoylphorbol-13-acetate that AP-1 and CREB are involved in the glucocorticoid activation of TRH gene expression in hypothalamic cultures.
To determine whether c-fos/c-jun (AP-1) and CREB mediate glucocorticoid stimulated TRH gene regulation, we investigated the effect of N-ethyl-maleimide (NEM), an alkylating agent, and 12-O-tetradecanoylphorbol-13-acetate (TPA) on this process. NEM decreased while TPA increased TRH levels in rat hypothalamic culture, changes similar to their effects on CREB and Fos/Jun proteins in the AtT20 cell line. This suggests that glucocorticoid stimulation of TRH gene expression may be regulated by the AP-1 complex and CREB pathway.
Luo
L G
LG
Division of Endocrinology, Brown University School of Medicine, Rhode Island Hospital, Providence 02903, USA.
Wang
S
S
Su
E
E
Jackson
I M
IM
D000818:Animals; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D019281:Dimerization; D005033:Ethylmaleimide / Q000494:pharmacology*; D005333:Fetus; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D016762:Genes, fos; D016758:Genes, jun; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D017362:Cyclic AMP Response Element-Binding Protein; D018808:Transcription Factor AP-1; D013973:Thyrotropin-Releasing Hormone; D003907:Dexamethasone; D013755:Tetradecanoylphorbol Acetate; D005033:Ethylmaleimide