Stress-induced stimulation of pituitary POMC gene expression is associated with activation of transcription factor AP-1 in hypothalamus and pituitary.

The response to environmental stimuli such as stress involves changes in gene transcription in both brain and pituitary, which in turn, facilitate adaptive phenotypic alterations favoring survival. In the present study we have examined the expression of the inducible immediate-early genes of the fos and jun families, and the activity of transcription factor AP-1 in the hypothalamus and anterior pituitary gland of rats, after a single restraint challenge. Restraint led to a rapid transient increase in c-fos but not c-jun expression in hypothalamus and pituitary. Changes in jun-B expression in hypothalamus were qualitatively similar to c-fos, though not statistically significant at 30 min. Furthermore, a single episode of restraint stress led to significant increases (50-100%) in nuclear AP-1 DNA binding activity in both hypothalamus and pituitary, while DNA binding of an unrelated transcription factor (Sp1) was unchanged. Associated with the stress-induced activation of pituitary AP-1 was a parallel three- to fourfold transcriptional stimulation of pituitary POMC gene expression. These data demonstrate that the rapidly inducible members of the fos and jun gene families contribute to increased activity of transcription factor AP-1 in both hypothalamus and pituitary following stress, and suggest that AP-1 may be a crucial factor involved in rapid transcriptional responses during stress.