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

• Published in: The European journal of neuroscience 2001-07, Vol.14 (1), p.1-9
• Main Authors: Stehle, Jörg H., Von Gall, Charlotte, Korf, Horst-Werner
• Format: Article
• Language: English
• Subjects: Animals; cAMP-signalling pathway; Circadian Rhythm - physiology; CREB; Cyclic AMP Response Element Modulator; Cyclic AMP Response Element-Binding Protein - metabolism; DNA-Binding Proteins - metabolism; Gene Expression Regulation - physiology; Humans; ICER; melatonin; Pineal Gland - cytology; Pineal Gland - metabolism; Repressor Proteins; Signal Transduction - physiology; Transcription Factors - metabolism
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1046/j.0953-816x.2001.01627.x

In neurons, a temporally restricted expression of cAMP‐inducible genes is part of many developmental and adaptive processes. To understand such dynamics, the neuroendocrine rodent pineal gland provides an excellent model system as it has a clearly defined input, the neurotransmitter norepinephrine, and a measurable output, the hormone melatonin. In this system, a regulatory scenario has been deciphered, wherein cAMP‐inducible genes are rapidly activated via the transcription factor phosphoCREB to induce transcriptional events necessary for an increase in hormone synthesis. However, among the activated genes is also the inhibitory transcription factor ICER. The increasing amount in ICER protein leads ultimately to the termination of mRNA accumulation of cAMP‐inducible genes, including the gene for the Aa‐nat that controls melatonin production. This shift in ratio of phosphoCREB and ICER levels that depends on the duration of stimulation can be interpreted as a self‐restriction of cellular responses in neurons and has also been demonstrated to interfere with cellular plasticity in many non‐neuronal systems.