OBJECTIVE: Glucocorticoid sensitivity varies between individuals and between tissues in the same individual. Although some of this variation is explained by the activity of the 11 beta-hydroxysteroid dehydrogenase enzymes, the possibility that glucocorticoid receptor sensitivity is modulated remains unexplored. This study examined glucocorticoid receptor binding in leucocytes and assessed the effects of seasonal hormonal variation on receptor binding. PATIENTS AND MEASUREMENTS: Two populations were studied. In the first, 318 healthy subjects were studied over 2 years with a single measurement of receptor binding made on each. In the second study nine healthy male subjects each had receptor binding measurements made at 3-week intervals over 1 year. RESULTS: In both populations there was significant seasonal variation in receptor binding. In the first population Kd for dexamethasone was highest in November and lowest in July (8.37 +/- 0.5 nmol/l vs. 1.58 +/- 0.7, mean +/- SEM P < 0.00001) and the number of receptor sites per leucocyte was highest in January and lowest in June (10 440 +/- 580 vs. 4969 +/- 302, P < 0.00001). In multivariate analysis, climate was the main determinant for both Kd and the number of receptor sites per cell: increases in day length and environmental temperature reduced Kd and the number of receptor sites per cell. Co-incubation with physiological concentrations of melatonin raised Kd without affecting receptor number. Co-incubation with forskolin lowered Kd suggesting that melatonin might act through the ML1 receptor class by inhibiting adenylyl cyclase. No correlations were found with 0900 h plasma cortisol. CONCLUSIONS: The results suggest that the glucocorticoid receptor might be modulated by season. Melatonin might mediate part of these effects. The lack of correlation with cortisol suggests that it is not an important determinant of receptor binding and that leucocyte receptors are regulated differently from central receptors.
OBJECTIVE: Glucocorticoid sensitivity varies between individuals and between tissues in the same individual. Although some of this variation is explained by the activity of the 11 beta-hydroxysteroid dehydrogenase enzymes, the possibility that glucocorticoid receptor sensitivity is modulated remains unexplored. This study examined glucocorticoid receptor binding in leucocytes and assessed the effects of seasonal hormonal variation on receptor binding. PATIENTS AND MEASUREMENTS: Two populations were studied. In the first, 318 healthy subjects were studied over 2 years with a single measurement of receptor binding made on each. In the second study nine healthy male subjects each had receptor binding measurements made at 3-week intervals over 1 year. RESULTS: In both populations there was significant seasonal variation in receptor binding. In the first population Kd for dexamethasone was highest in November and lowest in July (8.37 +/- 0.5 nmol/l vs. 1.58 +/- 0.7, mean +/- SEM P < 0.00001) and the number of receptor sites per leucocyte was highest in January and lowest in June (10 440 +/- 580 vs. 4969 +/- 302, P < 0.00001). In multivariate analysis, climate was the main determinant for both Kd and the number of receptor sites per cell: increases in day length and environmental temperature reduced Kd and the number of receptor sites per cell. Co-incubation with physiological concentrations of melatonin raised Kd without affecting receptor number. Co-incubation with forskolin lowered Kd suggesting that melatonin might act through the ML1 receptor class by inhibiting adenylyl cyclase. No correlations were found with 0900 h plasma cortisol. CONCLUSIONS: The results suggest that the glucocorticoid receptor might be modulated by season. Melatonin might mediate part of these effects. The lack of correlation with cortisol suggests that it is not an important determinant of receptor binding and that leucocyte receptors are regulated differently from central receptors.
Authors: Rogier A Quax; Laura Manenschijn; Jan W Koper; Johanna M Hazes; Steven W J Lamberts; Elisabeth F C van Rossum; Richard A Feelders Journal: Nat Rev Endocrinol Date: 2013-10-01 Impact factor: 43.330