The cortisol awakening response is related with PERIOD1 clock gene expression in older women

The cortisol awakening response (CAR) is a useful endocrine marker for the hypothalamic-pituitary-adrenal axis activity. Recent studies suggest that the cortisol level influences the expression of the hPER1 clock gene which is involved in the generation of biological rhythms. This study aimed to analyze the relationship between CAR and hPER1 gene expression with respect to human aging.

Salivary cortisol levels were determined in 20 older women (mean age ± SD, 67.9 ± 5.12 yrs) and 30 young women (24.4 ± 2.13 yrs) at awakening (T0) and at 15 min, 30 min, 45 min, and 60 min after awakening (T15, T30, T45, T60) by enzyme linked immunosorbent assay. CAR was calculated as difference of the cortisol levels at T0 and T30. The expression of the hPER1 gene at 0800 h was determined from oral mucosa cells by relative quantification using h36B4 as house-keeping gene. Additional variables, which may affect the CAR, were assessed by questionnaire. Relationships between CAR and other variables were analyzed by correlation and regression analyses.

Older women showed significantly lower mean cortisol levels than young women at all five time points (P < 0.05 to P < 0.01). The cortisol levels at T30, T45, and T60 correlated positively and significantly with hPER1 gene expression in older women (each, P < 0.01), but not in young women. In both older and young women, the CAR correlated positively with the hPER1 gene expression. This relationship was very strong in older women (r = -0.90, P<0.001) and non-significant in young women (r = 0.33, P = 0.390). Regression analysis showed that hPER1 gene expression was the only significant predictor of CAR (r² = 0.798, SEM = 0.07, P < 0.001) in older women.

The present study documents the influence of cortisol secretion on hPER1 gene expression in older women. The morning cortisol increase as indicated by CAR correlated positively and significantly with hPER1 gene expression in older women suggesting that hPER1 expression increases in response to the morning cortisol increase in older women. The higher hPER1 response to cortisol increase in older women could be due to the finding that the hPER1 response to cortisol increase seems to be sensitive only at low cortisol levels, but not at higher cortisol levels. This would explain why the older women with low cortisol levels showed an increase of hPER1 expression with increasing cortisol level, whereas young women with higher cortisol levels did not.