Abstract
Hormones control the major biological functions of stress response, growth, metabolism and reproduction. In animals these hormones show pronounced seasonality, with different set-points for different seasons. In humans, the seasonality of these hormones remains unclear, due to a lack of datasets large enough to discern common patterns and cover all hormones. Here, we analyze an Israeli health record on 46 million person-years, including millions of hormone blood tests. We find clear seasonal patterns: the effector hormones peak in winter-spring, whereas most of their upstream regulating pituitary hormones peak only months later, in summer. This delay of months is unexpected because known delays in the hormone circuits last hours. We explain the precise delays and amplitudes by proposing and testing a mechanism for the circannual clock: the gland masses grow with a timescale of months due to trophic effects of the hormones, generating a feedback circuit with a natural frequency of about a year that can entrain to the seasons. Thus, humans may show coordinated seasonal set-points with a winter-spring peak in the growth, stress, metabolism and reproduction axes.
- Systems endocrinology
- systems medicine
- hypothalamic-pituitary-adrenal axis
- gonadal axis
- thyroid axis
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
We added new figures on the time-of-day of all tests in each season, new modelling on circannual clock mechanisms, comparisons to animal studies, main-text figures on blood chemistry seasonality, information on methods, and improved the discussion.