Hormones, rhythms and brain function

shannon smith houle

What do breast cancer and jet lag have in common?

Both may have something to do with a mismatch between our internal clocks and the world around us, according to Concordia psychology professor Shimon Amir. This mismatch may affect women differently than it affects men.

“The interaction between circadian rhythms and the cell cycle [the process of cell division] may be particularly relevant in the context of cancer, particularly breast cancer.”

Circadian rhythms, our internal patterns of waking, sleeping and behaving, are Amir’s area of expertise. He has been studying circadian clocks, the internal timekeepers found in our brain and other organs, for over 10 years.

Recently Amir has been looking at how these clocks work differently in the female brain, compared to the male brain, at least in the rat.

“Male rats are fairly predictable animals. Each day looks like the next. For female rats, each day is different.”

That is because female rats have a four-day cycle, called the estrus cycle. Levels of ovarian hormones, including estrogen and progesterone, change in a distinctive pattern over the course of this cycle.

Amir, along with Concordia professor Jane Stewart, had been looking at one of the genes that make up our biological clocks, a gene called PER2. When he located the gene in brain structures known to be sensitive to ovarian hormones, he was curious.

“Do oscillators (circadian clocks) look the same in the female brain as in the male brain?”

That question led Amir, graduate student Jennifer Perrin and Concordia professor Barbara Woodside to look at how ovarian hormones affect circadian clock gene expression.

“We found that the oscillators in female rats depend on the phase of the estrus cycle.”

In at least two brain structures, the levels of the clock gene PER2 were the same as in male rats on some days, but on others, female rats showed a very different pattern of PER2 levels.

The research team then looked at rats that had had their ovaries removed and no longer had a hormone cycle. Those animals showed the same PER2 levels as male rats, but when they received injections of  estrogen the female pattern of PER2 levels returned.

“It all depends on hormones.” The two brain structures they looked at are linked to motivation and emotion.

“In general, the fact that we have circadian oscillators in areas that are important for motivation and emotion may help us understand phenomenon such as jet lag, problems associated with rotational shift work, and disruption in vigilance and affect in pathologies such as depression.”

Jet lag is caused by the desynchronization between an internal master clock and the light-dark cycle in the outside world. Once those  resynchronize, there is a mismatch between the multiple internal  clocks as they all try to catch up to the master clock. These  internal clocks are found in many areas of the brain as well as in organs outside of it.

“This is why we can experience emotional, cognitive and gastro-intestinal disturbances when we travel. And the same is true for rotational shift work.”

Since hormones affect these clocks, jet lag and shift work may have different effects on women’s brains and behaviour than they do in men.

Researchers have recently discovered that disrupted clock gene function can lead to cancer in mice. Other research indicates that clock genes are disrupted in the cells in breast cancer tumours.

Even though Amir’s work may be able to help link breast cancer to circadian rhythm disruption through the action of hormones, Amir points out that there is still a lot of work to be done before that happens.

“As much as we know, there is almost as much that we don’t know.”

Amir’s study was published in the proceedings of the National Academy of Sciences last month.