抄録
Hypothalamic hormones including dopamine regulate critical functions of pituitary cells via the cyclic AMP-protein kinase A (PKA) pathway. The PKA-downstream transcription factor cAMP response element-binding protein (CREB) is an integrating molecule activated by many other protein kinase pathways. We investigated the involvement of CREB in the regulation of cell proliferation and the PRL promoter of rat lactotrophs in primary cell culture. Adenoviruses were used for efficient gene delivery into pituitary cells. Bromocriptine, a dopaminergic agonist known to decrease intracellular cAMP concentrations, caused inhibition of PRL promoter activity and lactotroph proliferation, which was accompanied by decreases in CRE-mediated transcription and CREB phosphorylation in lactotrophs. Expression of a dominant-negative CREB (MCREB), which was effective in suppressing CRE-mediated transcription induced by forskolin, inhibited basal and forskolin-induced PRL promoter activity. MCREB expression lowered basal proliferative levels and blocked forskolin-induced proliferation of lactotrophs. IGF-1 did not affect intracellular cAMP concentrations but transiently increased lactotroph CREB phosphorylation. MCREB expression also inhibited IGF-1-induced lactotroph proliferation. These results suggest that CREB is involved in the regulation of cell proliferation and the PRL promoter in normal lactotrophs. [J Physiol Sci. 2007;57 Suppl:S172]
