REHOVOT, ISRAEL—February 2, 2021—Our minds may be affected by winter’s long nights or spring and its flowers, but what about our bodies? A new study at the Weizmann Institute of Science reveals that our hormones also follow a seasonal pattern. By analyzing data on several types of hormones from millions of blood tests, the researchers discovered that some hormones peak in winter or spring and others in summer. This research, which was published in the Proceedings of the National Academy of Sciences (PNAS), provides a broad, dynamic picture of hormone production – covering those connected to fertility, for example, but also hormones such as cortisol, which are mostly short-lived and not thought to be seasonal.
Alon Bar led the study together with Avichai Tendler; both are research students in Prof. Uri Alon’s group at the Institute’s Department of Molecular Cell Biology. Prof. Alon and his team have developed mathematical tools for uncovering patterns in big biological data, so when a study that was focused on a single hormone – cortisol – started to reveal a surprising seasonal pattern, the researchers decided to see whether other hormones might also fluctuate seasonally. They turned to Prof. Amos Tanay of Weizmann’s Department of Computer Science and Applied Mathematics, who has access to a database maintained by Clalit, Israel’s largest HMO. Clalit has broken new ground by creating a database that enables researchers to conduct large-scale biomedical studies on health data, while fully preserving the subjects’ anonymity.
The team analyzed the hormone levels in men and women between the ages of 20 and 50, in millions of blood tests sorted according to the months of the year. The scientists estimated that they had ultimately analyzed 46 million person-years; the results for each hormone were averaged from up to six million different blood tests. The researchers tracked 11 hormones, including cortisol (a stress hormone released by the adrenal glands), a thyroid hormone, reproduction and sex-based hormones, and a growth hormone produced in the liver.
On average, all of the hormones exhibited peaks and dips over the course of a year with a seasonal variation of around five percent, but the surprise was the ways in which certain hormones peaked at different times. For example, testosterone and estradiol – hormones more prevalent in men and women, respectively – were mirror images of one another. That is, in men, testosterone peaked in January and again, but a bit lower, in August; in women, estradiol followed the same pattern. In contrast, testosterone in women and estradiol in men peaked closer to April and dipped in the summer. So the fact that more children are conceived in certain seasons may have more to do with hormone balances than the blooming of flowers in the fields, says Bar.
The difference between hormones that peak in winter-spring and those that wait for summer was more confusing, especially as those that peak later in the year – in summer – tend to be the hormones that control the first kind. These hormones are produced in the pituitary, at the base of the brain, and send messages to the reproductive organs, adrenal glands, and others organs that then affect or control bodily functions or reactions.
These second hormones are called effector hormones – that is, hormones that act directly on the body – and the researchers devised a mathematical model to explain why the two types of hormones, which are directly related, should have different high and low seasons. Effector hormones such as cortisol and the pituitary hormones, explains Bar, affect not just the body’s metabolism and functions, but the masses of the organs themselves that secrete the hormones. That is, the pituitary hormones that stimulate the adrenal glands to produce cortisol also cause these glands to grow. But the cortisol produced in the adrenals causes the pituitary to shrink, thus eventually reducing the amount of stimulation to the adrenals, which shrink back down, and so on in a continual loop. The dynamic growth and shrinkage of such glands is a known phenomenon, and the researchers were able to link studies measuring the glands to the hormone fluctuations they had observed. Because the entire process takes place gradually over weeks and months, it creates a time lag from winter to summer and back again, and this explains the differences in peaks between the two groups of hormones.
While the exact cause of this cycle was not the subject of the study, the team believes that melatonin – a hormone triggered by light and dark that is produced in the brain – is most likely the “hand” that sets this year-long clock in motion. Assuming that this is the case, they would expect that, compared to the Israeli population, the patterns they found would be six months earlier (or later) in the Southern Hemisphere and that stronger peaks and valleys would be found in the population living farther north, where day length between seasons – and, thus, melatonin production – differs by much more than in Israel. “If we saw a five percent difference in Israel, that could be over 15 percent in Northern Europe,” says Bar – and indeed, the team found some evidence in the literature on cortisol from the UK, Sweden, and Australia to support this idea.
“It is not so surprising that our hormones have seasonal cycles,” adds Prof. Alon. “Many animals living in temperate climates have strong cycles, for example, all giving birth in the same season. We think that our hormonal systems have ‘set points’ that produce peaks, for example, in stress or reproductive hormones, and these may be adaptations that evolved to help us cope with seasonal changes in our surrounding environment.”
Prof. Uri Alon’s research is supported by the Sagol Institute for Longevity Research; the Jeanne and Joseph Nissim Center for Life Sciences Research; the Braginsky Center for the Interface Between Science and the Humanities; the Kahn Family Research Center for Systems Biology of the Human Cell; the Zuckerman STEM Leadership Program; the Rising Tide Foundation; the estate of Olga Klein-Astrachan; and the European Research Council. Prof. Alon is the incumbent of the Abisch-Frenkel Professorial Chair.