Diurnal patterns for cortisol, cortisone and agouti-related protein in human cerebrospinal fluid and blood

SK Panigrahi, CD Toedesbusch… - The Journal of …, 2020 - academic.oup.com
SK Panigrahi, CD Toedesbusch, JS McLeland, BP Lucey, SL Wardlaw
The Journal of Clinical Endocrinology & Metabolism, 2020academic.oup.com
Context Cortisol in blood has a robust circadian rhythm and exerts potent effects on energy
balance that are mediated in part by central mechanisms. These interactions involve
orexigenic agouti-related protein (AgRP) neurons that are stimulated by glucocorticoids.
However, diurnal changes in brain or cerebrospinal fluid (CSF) cortisol and cortisone, which
are interconverted by 11ß-HSD1, have not been characterized in humans. Objective To
conduct a secondary analysis of existing samples to characterize diurnal changes in cortisol …
Context
Cortisol in blood has a robust circadian rhythm and exerts potent effects on energy balance that are mediated in part by central mechanisms. These interactions involve orexigenic agouti-related protein (AgRP) neurons that are stimulated by glucocorticoids. However, diurnal changes in brain or cerebrospinal fluid (CSF) cortisol and cortisone, which are interconverted by 11ß-HSD1, have not been characterized in humans.
Objective
To conduct a secondary analysis of existing samples to characterize diurnal changes in cortisol and cortisone in CSF and examine their relationships to changes in AgRP.
Methods
Stored CSF and plasma samples were obtained from 8 healthy subjects who served as controls for a sleep study. CSF was collected every 2h for 36h via indwelling lumbar catheter; plasma was collected every 2h.
Results
There was a diurnal rhythm for cortisol and cortisone in CSF that closely followed the plasma rhythm by 2 h with peak and nadir levels at 0900h and 0100h. The ratio of cortisol (active) to cortisone (inactive) in CSF was 48% higher at the peak versus nadir. There was a diurnal rhythm for AgRP in plasma that was out of phase with the cortisol rhythm. There was a less distinct diurnal rhythm for AgRP in CSF that oscillated with a similar phase as cortisol.
Conclusions
There is a robust diurnal rhythm for cortisol and cortisone in CSF. Diurnal changes were noted for AgRP that are related to the cortisol changes. It remains to be determined if AgRP mediates adverse metabolic effects associated with disruption of the cortisol circadian rhythm.
Oxford University Press