Department of Molecular Cell Biology, Weizmann Institute of Science, 76100 Rehovot, Israel.
Department of Computer Science, Weizmann Institute of Science, 76100 Rehovot, Israel.
Proc Natl Acad Sci U S A. 2021 Feb 16;118(7). doi: 10.1073/pnas.2003926118.
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.
激素控制着应激反应、生长、代谢和生殖等主要生物学功能。在动物中，这些激素表现出明显的季节性，不同季节有不同的设定点。在人类中，由于缺乏足够大的数据集来识别常见模式并涵盖所有激素，这些激素的季节性仍不清楚。在这里，我们分析了以色列的 4600 万人年的健康记录，其中包括数百万人的激素血液检测。我们发现了明显的季节性模式：效应激素在冬春季达到峰值，而它们的大多数上游调节垂体激素仅在几个月后，即夏季达到峰值。这种数月的延迟是出乎意料的，因为已知激素回路中的延迟仅持续数小时。我们通过提出并测试一个关于年节律钟的机制来解释这种精确的延迟和幅度：由于激素的营养作用，腺体质量会以数月为时间尺度增长，从而产生一个具有约 1 年自然频率的反馈回路，该回路可以与季节同步。因此，人类可能在生长、应激、代谢和生殖轴上表现出协调的季节性设定点，冬季-春季达到峰值。
