Clocks and steroids interaction across the life span.

Abstract

The circadian system enables organisms to anticipate daily environmental changes and to align physiology and behaviour with the external light-dark cycle. In mammals, this temporal organisation is coordinated by the central pacemaker in the suprachiasmatic nucleus (SCN), which synchronises peripheral clocks through humoral and neural signals throughout the body. The circadian clock and steroid hormones are linked through a reciprocal, multi-level regulatory relationship. While the SCN and peripheral clocks shape the temporal pattern of steroid secretion, steroid hormones feed back onto the SCN and peripheral clocks, thereby modifying clock gene expression, phase, amplitude, synchrony, and network coherence. This interaction is dynamic across the lifespan, as both the clock and the steroid environment change during development, reproductive life, and ageing. During prenatal and early postnatal development, maternal glucocorticoids (GCs) and other perinatal steroid signals provide time-dependent cues that may shape the maturation and long-term function of the circadian system. During reproductive life in females, ovarian steroids dynamically remodel clocks within the hypothalamic-pituitary-ovarian (HPO) axis, coordinating reproductive timing with circadian signals from the SCN. In parallel, GCs interact with the reproductive axis and may influence fertility in a time-of-day- and cycle-stage-dependent manner. Disruption of this temporal coordination, for example, by shift work, may impair reproductive and endocrine function. With advancing age, both circadian and endocrine rhythms lose robustness, leading to weakened coordination between the SCN and peripheral clocks, as well as reduced synchrony among cellular clocks within peripheral tissues. These changes contribute to disturbed sleep-wake rhythms, reproductive ageing, and altered stress responsiveness. This review discusses the interaction between steroid hormones and circadian clocks across the life span, highlighting reciprocal regulation as a key mechanism linking temporal organisation to physiology and health.