Transcriptional regulation of interleukin-6 in pituitary folliculo-stellate TtT/GF cells.

Interleukin-6 (IL-6) secreted by pituitary folliculo stellate (FS) cells plays an important role in the control of pituitary function and proliferation. We demonstrate that in FS TtT/GF cells, estradiol (E(2)) inhibits dose dependently pituitary adenylate cyclase activating polypeptide (PACAP)-stimulated IL-6 secretion and transcription. We studied transcription factors involved in IL-6 stimulation by PACAP. Point mutations in kappaB, TRE, NF-IL-6 and CRE sites in the IL-6 promoter show that PACAP stimulates IL-6 through TRE and CRE sites. Accordingly, PACAP stimulated AP-1 and CREB transcriptional activity and E(2) inhibited TRE-LUC but not CRE-LUC activation. Thus, we demonstrate that transcription factors of the CREB and AP-1 family are critical for the stimulation of IL-6 by PACAP in TtT/GF cells and that estrogens block this stimulation by inhibiting AP-1 activity. The regulatory elements involved in IL-6 transcription in TtT/GF FS cells contribute to understand the specificity of the anterior pituitary gland paracrine pathways.