Circadian expression of nuclear receptors

First 'encyclopedia' of nuclear receptors reveals organisms' focus on sex, food:

Organisms thrive on sex and food, and so do their cells' receptors.

In creating the first "encyclopedia" of an entire superfamily of nuclear receptors - proteins that turn genes on and off throughout the body - UT Southwestern Medical Center researchers found that certain receptors form networks and interact to regulate disease states and physiology in two main areas, reproduction and nutrient metabolism.

Receptor networks also have key roles in metabolism's biological clock, researchers found.

The findings, published today in two studies in the journal Cell, chart the anatomy and timing of nuclear receptor expression throughout the body in hopes that researchers can uncover global receptor functions to improve prediction, diagnosis and treatment of diseases, from hypertension to diabetes.

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In the circadian study, researchers used mice to see how daily circadian rhythms influence the activity of the nuclear receptor superfamily in key metabolic tissues.

They found that the activity of more than half of receptors follow rhythmic cycles, so coordinated changes in receptor activity helps explain the cyclic behavior of metabolism. This also suggests that the superfamily acts as a mega-network to influence metabolism, rather than in a series of independent signaling pathways.

"Understanding timing patterns of receptors might help explain aspects of the out-of-rhythm states linked to many metabolic diseases," Dr. Mangelsdorf said.

Expression of receptors and expression of genes that are involved in synthesis and secretion of ligands that activate those receptors are synchronized by the circadian clock. This is sometimes called "internal coincidence".

When you are jet-lagged, some organs reset their timing to the new time-zone much faster than the others, leading to internal desynchronizaton. Thus, ligands (e.g., hormones) are secreted at times when their receptors are not around, and the receptors are expressed when there are no ligands in the system. Everything goes out of whack.

That is why jet-lag makes you feel sick, and a permanent state of being jet-lagged caused by shift-work (so called "shift-lag") can make you seriously ill.

It is not just nuclear receptors that are expressed in a rhythmic fashion. If a gene is important for the function of that cell, i.e., not housekeeping genes (e.g., actin or ribosome subunits) but genes that define that cell's "job" in the body (e.g., liver enzymes in liver cell, neurotransmitters in neurons, etc.), than that gene will be expressed in a circadian pattern.

The map of nuclear receptors will be a great aid for future research in circadian regulation of body functions.

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Thank you, that's exciting. It makes sense, and isn't new, that organs reset at different rates after trans-meridian travel; after a few days, everything is in sync. What I don't understand is why "shift-lag" doesn't likewise go away when a person works and lives on an 'abnormal' shift consistently.
Having DSPS and working days, I've done shift work all my life and it's taking its toll. OK, it's not just like shifting time zones, as I used to sleep 2 shifts per day to make it work...
(My blog is all about DSPS.)

Rotating shifts are obvious in their way of making us jet-lagged. A constant night shift could, in theory, work fine, except that exposure to light and social pressures (family, etc.) tend to constantly pull the clock to synchronize with the planet instead of the night-shift. So night-shift workers are constantly going back-and-forth between two (or more) schedules, e.g., one for workweek, another for weekends, thus producing permanent jet-lag.

OK, thanks. "A constant night shift could, in theory, work fine..." was what I wanted to see confirmed.
In fact I know (of) a man who does it, a DSPSer. Bedtime is 1 pm, 7 days a week. Work is from midnight, 5 nights a week. He says that after he got his wife trained to really accept it, it works fine.

Yes. It works in rare situation of social isolation, where individuals or groups are kept separate from the rest of society in artificial light-dark cycles and artificial schedules, e.g., in research bunkers, in Biosphere, on submarines, on space stations, etc. It is the pull of the family, friends, TV, etc., that makes night-shift a cause of continuous jet-lag.