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-I) and CREB mediate glucocorticoid sti mulated TRH gene regulation, we investigated the effect of N-ethyl-maleimid e (NEM), an alkylating agent, and 12-O-tetradecanoylphorbol- 13-acetate (TP A) on this process. NEM decreased while TPA increased TRH levels in rat hyp othalamic culture, changes similar to their effects on CREB and Fos/Jun pro teins in the AtT20 cell line. This suggests that glucocorticoid stimulation of TRH gene expression may be regulated by the AP-1 complex and CREB pathw ay. (C) 1999 Elsevier Science B.V. All rights reserved.