BIOLOGY 3UU3 Lecture Notes - Camp-Dependent Pathway, Per1, Circadian Clock

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9 Feb 2013
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Article 4
Rhythmic gene expression in pituitary depends in herterologous sensitization by the
neurohormone melatonin
Abstract
-mammalian daily cycles are driven by a circadian clock
-clock is based on the cell-autonomous rhythmic expression of clock genes
-cycling expression of Period 1 (a clock gene) in the pituatory gland depends on
heterologous sensitization of the adenosine A2b receptor
-this happens by the nighttime activation of the melatonin mt1 receptors
-eliminating melatonin suppresses the expression of Period 1 and increases the release of
prolactin from the pituitary
Introduction
-if gene expression in not temporally correct, cellular malfunction and disease can result
-hypothalamic suprachiasmatic nucleus (SCN):
-partitions metabolic functions in 24 hour cycle
-24 hour rhythm is regulated by transcription/translation feedback loops
-PERIOD in humans in a transcription/translation feedback loop
-PERIPHERAL RHYTHMS:
-circadian rhythms are not limited to the cells of the SCN, they can be found in
many tissues, but with a delayed timing with respect to the SCN
-peripheral rhythms dampen in vitro after a few cycles b/c they depend on
neuronal and/or neuroendocrine signals from the SCN
-when the SCN and peripheral clock-controlled genes are not in synch, jet-lag and
shift-work pathologies result
-both neural and endocrine pathways can maintain circadian gene expression in
the periphery:
-Period (Per) gene rhythms can be regulated by glucocorticoids and cycles
of restricted feeding in rodents
-in rodent pineal gland: Per1 activity is sustained by noradrenergic
activation of the cyclic AMP pathway
-CYCLIC AMP PATHWAY:
-sustains rodent Per1 activity
-drives synthesis of pineal melatonin (which has neuroendocrine role in central
circadian clock)
-major coordinator of circadian and seasonal physiology
-HYPOPHYSEAL PARS TUBERALIS (PT):
-contains high density of receptors for melatonin
-implicated in expression of both circadian rhythm and seasonal endocrine cycles
-has clock genes with rhythms that are sensitive to time of day, and time of year
-melatonin is an important link between the central circadian pacemaker (SCN?) and the
PT (results in long-term modulation of prolactin levels)
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