Age and oestrus cycle-related changes in glucocorticoid excretion and wheel-running activity in female mice carrying mutations in the circadian clock genes Per1 and Per2

In mammals, numerous physiological and behavioural functions are controlled by an endogenous circadian clock located in the suprachiasmatic nuclei (SCN). Within the SCN neurons, clock genes such as Per1 and Per2 interact in a molecular clockwork regulating the expression of hundreds of output genes. Through the timed release of humoral and neuronal signals, the rhythmicity of numerous biological processes, including reproductive behaviour, the oestrus cycle and endocrine parameters is controlled by the SCN. Mutations in Per genes in mice affect a wide array of physiological functions. Interestingly, most of these studies use only male animals, thus neglecting potential gender-specificities in clock function. In an attempt to broaden this perspective we have investigated the impact of Per1 and Per2 mutations on both glucocorticoid (GC) metabolite excretion and locomotor activity in relation to age and oestrus cycle stage of female mice. We show that the Per2 mutation dampens daily GC rhythms in young adult females. While locomotor activity does not vary along the different oestrus stages in Per2 mutant females, oestrus effects on GC excretion and locomotor activity are largely comparable between Per1 mutants and wild-type animals. 20 month-old, acyclic Per1 and wild-type females show reduced GC levels when compared to young adults while aged Per2 mutants retain their normal GC rhythmicity. Correlating with this, onsets of locomotor activity do not change with age in Per2 mutant females. Together, our data highlight specific roles for Per1 and Per2 in both the regulation of locomotor activity and endocrine functions in the female organism. Crown