Cronobiologie

8/11/2019 Cronobiologie

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Cortisol circadian rhythmand its role in humanphysiology

Diana Loreta Paun, C. Dumitrache

C.I.Parhon National Institutue of Endocrinology, Bucharest,RomaniaCarol Davila University of Medicine and Pharmacy


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Cortisol

Cortisol is an essentialstress hormone and

deficiency leads to death.

Cortisol is an steroidhormone secreted by theadrenal gland and likemany other physiologicalprocesses in the body has

a circadian rhythm.


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Pacemaker

This rhythm isdistinct and isregulated by the

main circadianoscillator(pacemaker) in thesuprachiasmatic

nucleus (SCN) whichis located in thehypothalamus.


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Synchronization of circadianrhythms

Humans exhibit daily physiologicaland behavioural rhythms withnearly all body functions showing

significant daily variations; theseinclude sleep

body temperature

plasma concentrations of cortisol andgrowth hormone

urinary excretion of potassium

[Moore-Ede et al. 1983]
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475279/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475279/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475279/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475279/


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Synchronization of circadianrhythms

These circadian rhythms areproduced by endogenousprocesses referred to ascircadian oscillators which

coordinate and orchestratemolecular and physiologicalrhythms with changes in theenvironment [Dunlap, 1999].

The autonomic nervoussystem and endocrine signalsare the principal mediators ofthis internal rhythmicity

[Buijs and Kalsbeek, 2001].
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475279/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475279/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475279/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475279/


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The regulation of

glucocorticoid release The HPA axis receives input from the

central pacemaker which controls thecircadian release of corticotrophin-releasing hormone (CRH), this also

stimulated by physical and emotionalstressors. CRH in turn stimulates release of

adrenocorticotrophic hormones (ACTH)from the corticotroph cells in theanterior pituitary, and thence theglucocorticoid cortisol from the adrenalcortex.

In turn, cortisol exerts inhibitory effectsat pituitary and hypothalamic levels, ina classical negative feedback loop.

[Oster et al. 2006].


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Cortisol circadian rhythm

cortisol levels reachlowest levels ataround midnight

levels start to rise ataround 02:00 to03:00

reach a peak ataround 08:30

cortisol levels thenslowly decreaseback to the nadir tocomplete the cycle

over 24 h [Debono et al. 2009; Krieger et al.1971; Weitzman et al. 1971].
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475279/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475279/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475279/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475279/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475279/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475279/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475279/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475279/


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Timing

Infants are born without a circadianrhythm in cortisol and they acquire itduring their first year of life.

Studies do not agree on the age ofappearance of the circadian rhythm(varying between 2 weeks till the age

of 9 months) nor on whether it isrelated to the appearance of the sleepwake circadian rhythm.


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Cortisol production rate

A number of cortisol secretory episodes occurduring the 24 h of the day making it possible todescribe four different unequal temporal phases.


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Cortisol production rate

These phases are represented by: a period of minimal secretory activity, during which

cortisol secretion is negligible, and occurs 4 h prior to and2 h after sleep onset,

a preliminary nocturnal secretory episode at the thirdthrough fifth hours of sleep,

a main secretory phase of a series of three to five episodesoccurring during the sixth to eighth hours of sleep and

continuing through the first hour of wakefulness

an intermittent waking secretory activity of four to ninesecretory episodes found in the 212-h waking period.


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Ultradian Pulse

ACTH and cortisolare releasedepisodically in pulsesevery 20-30 minthroughout the day,but the amplitude of

these pulses aregreater in themorning.


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Factors involved in therhythm of ACTH and Cortisol

Intrinsic rhytmicity of the synthesis andsecretion of CRH and AVP by the

hypothalamus Feeding cycles

Light/dark and activity/rest cycles

Rhytmicity in the adrenal, possiblymediated by adrenal innervation


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Rhytmicity of hypothalamic CRH

Static and dynamicmeasures of CRH and AVP

synthesis show a diurnalrhythm that appears to beinherent in thehypothalamic cell bodies

Hypothalamic rhytmicityappears to be neuronal orintrinsec but not hormonal

Krieger DT Rhythms in CRF, ACTH and corticosteroids, 1979


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Feeding cycles

Concentrations of cortisolare highest beforebreakfast and additionalpeaks appear to be

coincident with lunch Although preprandial peaks

of cortisol are common,there are variable and do

not occur in subjectswhose normal patterns ofactivity do not includethese meals

Follenius, Diurnal cortisol peaks and their relationsships to meal, 1982


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Light/Dark cycles

The simplest correlation with thecircadian rhythms of ACTH andcortisol is light/dark cycles

Once the diurnal rhythm isestablished, it is not change easilyand persist after:

Prolonged bed rest Continuous feeding

2-3 day period of sleep deprivation

Krieger DT Rhythms in CRF, ACTH and corticosteroids, 1979


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Light/Dark cycles

This rhythm remainsunchanged in people whowork night shifts but maintainconventional hours onweekends

When individuals shiftsleep/waking, light/dark andfeeding schedules congruently

such as moving to a distanttime zonethe circadianrhythm of cortisol and ACTHchanges over the course of 3to 5 days.

Krieger DTRhythms in CRF, ACTH and corticosteroids, 1979


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Adrenal Rhyhmicity and OtherFactors

Adrenal activity appears toexhibit some diurnal

rhyhmicity that isindependent of CRH, AVP,and ACTH

this may reflect inherent

rhythmicity may be regulated via

adrenal innervation

Brandenberger G, 1984


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Control of cortisol

secretion A wide variety of physical and psychological

factors can alter the complex control of thediurnal variations of ACTH and cortisolsecretion.

These factors are mediated largely by thecentral nervous system.

Age does not appear to alter diurnal rhythmof cortisol but maximal concentrations ofcortisol occur earlier in the day in agedsubjects.

Sherman B, 1985


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Changes in the Diurnal Rhythmof cortisol

Cortisol secretion can beincreased by:

Mild fear or psychological

stress (anticipation ofvenipuncture)

Severe stress (preparationfor cardiac surgery)

Anticipation of a stress(athletic competition,university examination)

Sutton JR, 1975


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Psyhological stress and also major physicalstress such as: severe trauma

major surgery

severe illness fever

hypoglycemia

burns or exposure to cold

dehydration, hypotension irradiations

intensive exercise

can increase the secretion of cortisol.


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Chronic illnesses as congestive heartfailure or liver disease also alter the

diurnal rhythm of ACTH and cortisol. Patients with major depression have

increased basal cortisol as a result of a

blunting of the diurnal rhythm ofcortisol and ACTH similar to that seenin Cushings disease.


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Circulating cortisol is increased anddiurnal variations are decreased in

anorexia nervosa Cyproheptadine can inhibit rises inACTH and cortisol induced by

hypoglycemia.


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Conclusion

Cortisol has one of the mostdistinct and fascinating circadianrhythms in human physiology.

Cortisol acts as a secondarymessenger between central andperipheral clocks, hence its

importance in the synchronizationof body circadian rhythms.


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