Clock outputs and physiological rhythms Flashcards
Describe the rhythmic of Vasopressin (AVP) in the SCN and SON and what that tells us about clock controlled genes
SCN: High AVP during day and low at night, similar to Per1
However, was found in supraoptic nucleus at constant expression levels, independent of clock gene mutation
Tells us that the gene that encodes a clock controlled protein is not clock controlled everywhere
What was found when scanning all clock controlled genes?
A gene that’s rhythmic in one tissue is not necessarily rhytmic in another tissue
How many genes in a cell are rhythmic?
Nearly half
What is the effect of noradrenaline on melatonin production?
Where is NA released and what does this look like in health?
Promotion of AANAT (RLS in melatonin production)
In health, Pineal gland releases Noradrenaline rhythmically causing a spike of melatonin at night
Describe the SCN-periphery neuroendocrine pathways
SCN sends signals to PVN to release CRH in pituitary, which sends ACTH to the adrenal glands, which will rhythmically release corticosterone (blue path)
At the same time, SCN also connects to the adrenal glans neurally (via the PVN) which contributes to the production of corticosterone as well (red path)
What was found when comparing rhythmic transcripts in liver cells that had or didn’t have a functional liver clock?
Functional liver clock: most transcripts were rhythmic and acting normally
Inactivated liver clock: a few rhythmic transcripts do not need the local clock
Describe the experiment that proved corticosterone production was gated in adrenal cells
IN VIVO: no SCN signal
Two different mice types: wt and (local) clockless
Each group was sampled at two different times (CT0 and CT12) and treated ACTH, then corticosterone production was measured
wt: more corticosterone produced at CT12 compared to CT0
clockless: no difference
Conclusion - corticosterone production is gated: the clock within the gland either helps the tissue respond better at night, or respond not as well during the day
What was found with regards to metabolism in clockless mice?
lower insulin levels, poorer glucose tolerance, increased weight
Liver metabolite levels vary over the course of the day, therfore metabolism is rhythmic
Describe the rhythmic control along the hypothalami-pituitary-gonadal axis
SCN neurons release VIP and AVP rhythmically
VIP and AVP indirectly cause GnRH neurons to release GnRH into the median eminence and cause the anterior piruitary to release LH (AVP via ERalpha)
LH acts on Ovaries to release Estrogen
Estrogen feedsback to anterior pituitary and ERalpha
GnRH neurons and Anterior pituitary are slave oscillators
This is an example of gating
How is the cell cycle related to the circadian clock?
TTFL is very important in passing of cell checkpoints
People with faulty clocks may be at higher risk of cancer
