Analysis of cell signalling in the rodent pineal gland deciphers regulators of dynamic transcription in neural/endocrine cells

In neurons, a temporally restricted expression of cAMP-inducible genes is p art of many developmental and adaptive processes. To understand such dynami cs, the neuroendocrine rodent pineal gland provides an excellent model syst em as it has a clearly defined input, the neurotransmitter norepinephrine, and a measurable output, the hormone melatonin. In this system, a regulator y scenario has been deciphered, wherein cAMP-inducible genes are rapidly ac tivated via the transcription factor phosphoCREB to induce transcriptional events necessary for an increase in hormone synthesis. However, among the a ctivated genes is also the inhibitory transcription factor ICER. The increa sing amount in ICER protein leads ultimately to the termination of mRNA acc umulation of cAMP-inducible genes, including the gene for the Aa-nat that c ontrols melatonin production. This shift in ratio of phosphoCREB and ICER l evels that depends on the duration of stimulation can be interpreted as a s elf-restriction of cellular responses in neurons and has also been demonstr ated to interfere with cellular plasticity in many non-neuronal systems.