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Biological: Behavioural genetics · Evolutionary psychology · Neuroanatomy · Neurochemistry · Neuroendocrinology · Neuroscience · Psychoneuroimmunology · Physiological Psychology · Psychopharmacology (Index, Outline)
Hydrocortisone chemical structure | |
11,17,21-trihydroxy-,(11beta)- pregn-4-ene-3,20-dione IUPAC name | |
CAS number 50-23-7 |
ATC code H02AB09 (and others) |
PubChem 5754 |
DrugBank [1] |
Chemical formula | |
Molecular weight | 362.465 |
Bioavailability | |
Metabolism | |
Elimination half-life | |
Excretion | {{{excretion}}} |
Pregnancy category | C |
Legal status | |
Routes of administration | Oral tablets, intravenously, topical |
Hydrocortisone or Cortisol is a corticosteroid hormone produced by the zona fasciculata of the adrenal cortex (in the adrenal gland). It is a vital hormone that is often referred to as the "stress hormone" as it is involved in the response to stress.
- Main article: Cortisol and stress
It has a number of widespread physiological effects such as increasing blood pressure and blood sugar levels, and has an immunosuppressive action. With these sort of effects cortisol can be seen as a mediator between physical] and psychological stress and a number of psychosomatic disorders.
In pharmacology, the synthetic form of cortisol is referred to as hydrocortisone, and is used as an antagonist in the treatment of allergies and inflammation as well as substitute supplementation in cortisol production deficiencies. When first introduced as a treatment for rheumatoid arthritis, it was referred to as Compound E.
Physiology[]
The amount of cortisol present in the serum undergoes diurnal variation, with the highest levels present in the early morning, and the lowest levels present around midnight, 3-5 hours after the onset of sleep. Information about the light/dark cycle is transmitted from the retina to the paired suprachiasmatic nuclei in the hypothalamus. The pattern is not present at birth (estimates of when it starts vary from two weeks to 9 months).[1]
Changed patterns of serum cortisol levels have been observed in connection with abnormal ACTH levels, clinical depression, psychological stress, and such physiological stressors as hypoglycemia, illness, fever, trauma, surgery, fear, pain, physical exertion or extremes of temperature.
There is also significant individual variation, although a given person tends to have consistent rhythms.
Binding[]
Most serum cortisol, all but about 4%, is bound to proteins including corticosteroid binding globulin (CBG), and serum albumin. Only free cortisol is available to most receptors.
Regulation[]
The primary control of cortisol is the pituitary gland peptide, adrenocorticotropic hormone (ACTH). ACTH probably controls cortisol by controlling movement of calcium into the cortisol secreting target cells.[2]. ACTH is in turn controlled by the hypothalamic peptide, corticotropin releasing factor (CRF), which is under nervous control. CRF acts synergisticly with arginine vasopressin, angiotensin II, and epinephrine [3]. When activated macrophages start to secrete interleukin-1 (IL-1), which synergistically with CRF increases ACTH, [4] T-cells also secrete glucosteroid response modifying factor (GRMF or GAF) as well as IL-1, both of which increase the amount of cortisol required to inhibit almost all the immune cells [5]. Thus immune cells take over their own regulation, but at a higher cortisol set point. Even so, the rise of cortisol in diarrheic calves is minimal over healthy calves and drops below with time. [6] The cells do not lose all of the fight or flight override because of interleukin-1's synergism with CRF. Cortisol even has a negative feedback effect on interleukin-1 [7] which must be especially useful against those diseases which gain an advantage by forcing the hypothalamus to secrete too much CRF, such as the endotoxin bacteria..The suppressor immune cells are not affected by GRMF, [8] so that the effective set point for the immune cells may be even higher than the set point for physiological processes. GRMF (called GAF in this reference) primarily affects the liver rather than the kidneys for some physiological processes [9].
A high potassium media, which stimulates aldosterone secretion in vitro, also stimulates cortisol secretion from the fasciculata zone of dog adrenals [10] unlike corticosterone, upon which potassium has no affect [11]. Potassium loading increases ACTH and cortisol in people also [12]. This is no doubt the reason why a potassium deficiency causes cortisol to decline (as just mentioned) and why a potassium deficiency causes a decrease in conversion of 11deoxycortisol to cortisol [13]. This probably contributes to the pain in rheumatoid arthritis since cell potassium is always low in that disease [14]
Effects[]
- Main article: Physiological effects of cortisol
In normal release, cortisol (like other glucocorticoid agents) has widespread actions which help restore homeostasis after stress. (These normal endogenous functions are the basis for the physiological consequences of chronic stress - prolonged cortisol secretion.).
Factors affecting cortisol levels[]
Factors generally reducing cortisol levels[]
- Magnesium supplementation decreases serum cortisol levels after aerobic exercise,[15][16] but not in resistance training.[17]
- Omega 3 fatty acids, in a dose dependent manner (but not significantly),[18] can lower cortisol release influenced by mental stress[19] by suppressing the synthesis of interleukin-1 and 6 and enhance the synthesis of interleukin-2, where the former promote higher CRH release. Omega 6 fatty acids, on the other hand, acts inversely on interleukin synthesis.[citation needed]
- Music therapy can reduce cortisol levels in certain situations.[20]
- Massage therapy can reduce cortisol.[21]
- Laughing and the experience of humour can lower cortisol levels.[22]
- One study by a Japanese cosmetics company has asserted that makeup reduces cortisol levels in a mental stress situation.[23]
- Soy derived Phosphatidylserine interacts with cortisol but the right dosage is still unclear.[24][25]
- Vitamin C may slightly blunt cortisol release in response to a mental stressor.[26]
- Black tea may speed up recovery from a high cortisol condition.[27][28]
Factors generally increasing cortisol levels[]
- Caffeine may increase cortisol levels.[29]
- Sleep deprivation increases cortisol levels.[30]
- Intense (high VO2 max) or prolonged physical exercise stimulate cortisol release in order to increase gluconeogenesis and maintain blood glucose.[31] Proper nutrition[32] and high-level conditioning[33] can help stabilize cortisol release.
- Val/Val variation of the BDNF gene in men, and the Val/Met variation in women is associated with increased salivary cortisol in a stressful situation.[34]
- Hypoestrogenism and melatonin supplementation increases cortisol levels in postmenopausal women.[35]
- Burnout is associated with higher cortisol levels.[36]
- Severe trauma or stress events can elevate cortisol levels in the blood for prolonged periods.[37]
- Subcutaneous adipose tissue regenerates cortisol from cortisone.[38]
- Anorexia nervosa increases cortisol levels.[39]
- The serotonin receptor gene 5HTR2C is associated with increased cortisol production in men.[40]
- Some formulations of combined oral contraceptive pills increase cortisol levels in young women who perform whole-body resistance exercise training.[41]
- Commuting increases cortisol levels, related to the length of the trip, the amount of effort involved and the predictability of the trip[42]
Diseases and disorders[]
- Hypercortisolism: Excessive levels of cortisol in the blood result in Cushing's syndrome.
- Hypocortisolism, or adrenal insufficiency: If on the other hand the adrenal glands do not produce sufficient amounts of cortisol, Addison's disease is the consequence.
The relationship between cortisol and ACTH is as follows:
Plasma Cortisol | Plasma ACTH | |
---|---|---|
Primary Hypercortisolism (Cushing's syndrome) | ↑ | ↓ |
Secondary Hypercortisolism (pituitary, Cushing's disease) | ↑ | ↑ |
Primary Hypocortisolism (Addison's disease) | ↓ | ↑ |
Secondary Hypocortisolism (pituitary) | ↓ | ↓ |
Pharmacology[]
Hydrocortisone is the pharmaceutical term for cortisol used for oral administration, intravenous injection, or topical application. It is used as an immunosuppressive drug, given by injection in the treatment of severe allergic reactions such as anaphylaxis and angioedema, in place of prednisolone in patients who need steroid treatment but cannot take oral medication, and peri-operatively in patients on long-term steroid treatment to prevent an Addisonian crisis. It may be used topically for allergic rashes, eczema, psoriasis and certain other inflammatory skin conditions. It may also be injected into inflamed joints resulting from diseases such as gout.
Compared to prednisolone, hydrocortisone is about 1/4 the strength for the anti-inflammatory effect, while dexamethasone is about 40 times as strong as hydrocortisone. For side effects, see corticosteroid and prednisolone.
Hydrocortisone creams and ointments are available without prescription in strengths ranging from 0.05% to 2.5%, depending on local regulations, with stronger forms available with prescriptions only. Covering the skin after application increases the absorption and effect. Such enhancement is sometimes prescribed, but otherwise should be avoided to prevent over-dosing and systemic impacts.
Advertising for the dietary supplement CortiSlim originally (and falsely) claimed that it contributed to weight loss by blocking cortisol. The manufacturer was fined $1.2 million by the Federal Trade Commission in 2007 for false advertising, and no longer claims in their marketing that CortiSlim is a cortisol antagonist.[43]
Biochemistry[]
Biosynthesis[]
Cortisol is synthesized from cholesterol. The synthesis takes place in the zona fasciculata of the cortex of the adrenal glands. (The name cortisol comes from cortex.) While the adrenal cortex also produces aldosterone (in the zona glomerulosa) and some sex hormones (in the zona reticularis), cortisol is its main secretion. The medulla of the adrenal gland lies under the cortex and mainly secretes the catecholamines, adrenaline (epinephrine) and noradrenaline (norepinephrine) under sympathetic stimulation (more epinephrine is produced than norepinephrine, in a ratio 4:1).
The synthesis of cortisol in the adrenal gland is stimulated by the anterior lobe of the pituitary gland with adrenocorticotropic hormone (ACTH); production of ACTH is in turn stimulated by corticotropin-releasing hormone (CRH), released by the hypothalamus. ACTH increases the concentration of cholesterol in the inner mitochondrial membrane (via regulation of STAR (steroidogenic acute regulatory) protein). ACTH also stimulates the main rate-limiting step in cortisol synthesis where cholesterol is converted to pregnenolone, catalyzed by Cytochrome P450SCC (side chain cleavage enzyme).[44]
Metabolism[]
Cortisol is metabolized by the 11-beta hydroxysteroid dehydrogenase system (11-beta HSD), which consists of two enzymes: 11-beta HSD1 and 11-beta HSD2.
- 11-beta HSD1 utilizes the cofactor NADPH to convert biologically inert cortisone to biologically active cortisol.
- 11-beta HSD2 utilizes the cofactor NAD+ to convert cortisol to cortisone.
Overall the net effect is that 11-beta HSD1 serves to increase the local concentrations of biologically active cortisol in a given tissue, while 11-beta HSD2 serves to decrease the local concentrations of biologically active cortisol.
Cortisol is also metabolized into 5-alpha tetrahydrocortisol (5-alpha THF) and 5-beta tetrahydrocortisol (5-beta THF), reactions for which 5-alpha reductase and 5-beta reductase are the rate-limiting factors, respectively. 5-beta reductase is also the rate-limiting factor in the conversion of cortisone to tetrahydrocortisone (THE).
The CA3 area of hippocampus (memory) is affected by cortisol. [citation needed]
An alteration in 11-beta HSD1 has been suggested to play a role in the pathogenesis of obesity, hypertension, and insulin resistance, sometimes referred to the metabolic syndrome. [citation needed]
An alteration in 11-beta HSD2 has been implicated in essential hypertension and is known to lead to the syndrome of apparent mineralocorticoid excess (SAME).[citation needed]
See also[]
- Cushing's syndrome
- HPA axis
- ACTH stimulation test
- Hypopituitarism
- Post-traumatic stress disorder
- Central serous retinopathy
- CortiSlim
- Relacore, a pill which claims to reduce Cortisol.
Additional images[]
References[]
- ↑ de Weerth C, Zijl R, Buitelaar J (2003). Development of cortisol circadian rhythm in infancy. Early Hum Dev 73 (1-2): 39-52.
- ↑ Davies E. Keyon, C.J.; Fraser, R. (1985) "The role of calcium ions in the mechanism of ACTH stimulation of cortisol synthesis." Steroids 45: 557.
- ↑ Plotsky, P.M.; Sapolsky, Otto S., RM. (1986) "Inhibition of immunoreactive corticotropin-releasing factor secretion into the hypophysial portal circulation by delayed glucocorticoid feedback." Endocrinology 119: 1126,.
- ↑ Besedovsky, H.O.; Del Rey, A.; Sorkin, E. (1984) "Integration of Activated Immune Cell Products in Immune Endocrine Feedback Circuits." p. 200 in Leukocytes and Host Defense Vol. 5 [Oppenheim, J.J.; Jacobs, D.M., eds]. Alan R. Liss, New York,.
- ↑ Fairchild, S.L.; Shannon, K.; Kwan, E.; Mishell, R.I. (1984) "T-Cells Derived Glucocorticosteroid Lymphocytes and a T-Cell Hybridoma." Journal of Immunology 132: 821,.
- ↑ Dvorak, M.; "Plasma 17-Hydroxycorticosteroid Levels in Healthy and Diarrheic Calves." British Veterinarian Journal 127: 372, 1971.
- ↑ Besedovsky, H.O.; Del Rey, A.; Sorkin, E. (1984) "Integration of Activated Immune Cell Products in Immune Endocrine Feedback Circuits." p. 200 in Leukocytes and Host Defense Vol. 5 [Oppenheim, J.J.; Jacobs, D.M., eds]. Alan R. Liss, New York,.
- ↑ Fairchild, S.L.; Shannon, K.; Kwan, E.; Mishell, R.I. (1984) "T-Cells Derived Glucocorticosteroid Lymphocytes and a T-Cell Hybridoma." Journal of Immunology 132: 821,.
- ↑ Stith RD McCallum RE (1986) “General effect of endotoxin on glucocorticoid receptors in mammalian tissues. “ Circ. Shock 18(4); 301-309.
- ↑ Mikosha, A.S.; Pushkarov, I.S.; Chelnakova, I.S.; Remennikov, G.Y.A. (1991) “Potassium Aided Regulation of Hormone Biosynthesis in Adrenals of Guinea Pigs Under Action of Dihydropyridines: Possible Mechanisms of Changes in Steroidogenesis Induced by 1,4, Dihydropyridines in Dispersed Adrenocorticytes.” Fiziol. [Kiev] 37: 60,.
- ↑ Mendelsohn, F.A.; Mackie, C. (1975) “Relation of Intracellular K+ and Steroidogenesis in Isolated Adrenal Zona Glomerulosa and Fasciculata Cells.” Clinical Sci. Mol. Medical 49: 13,
- ↑ Ueda Y, Honda M, Tsuchiya M, Watanabe H, Izumi Y, Shiratsuchi T, Inoue T, Hatano M. (1982) “Response of plasma ACTH and adrenocortical hormones to potassium loading in essential hypertension.” Jpn Circ J. Apr;46(4):317-22.
- ↑ Bauman K Muller J 1972 “Effect of potassium on the final status of aldosterone biosynthesis in the rat. I 18-hydroxylation and 18hydroxy dehydrogenation. II beta-hydroxylation.” Acta Endocrin. Copenh. 69; I 701-717, II 718-730.
- ↑ LaCelle PL et al (1964) “An investigation of total body potassium in patients with rheumatoid arthritis.” Proceedings of the Annual Meeting of the American Rheumatism Association, Arthritis and Rheumatism 7; 321.
- ↑ PMID 6527092 (PMID 6527092)
Citation will be completed automatically in a few minutes. Jump the queue or expand by hand - ↑ PMID 9794094 (PMID 9794094)
Citation will be completed automatically in a few minutes. Jump the queue or expand by hand - ↑ DOI:10.1186/1550-2783-1-2-12
This citation will be automatically completed in the next few minutes. You can jump the queue or expand by hand - ↑ PMID 1832814 (PMID 1832814)
Citation will be completed automatically in a few minutes. Jump the queue or expand by hand - ↑ PMID 12909818 (PMID 12909818)
Citation will be completed automatically in a few minutes. Jump the queue or expand by hand - ↑ PMID 15086180 (PMID 15086180)
Citation will be completed automatically in a few minutes. Jump the queue or expand by hand - ↑ PMID 16162447 (PMID 16162447)
Citation will be completed automatically in a few minutes. Jump the queue or expand by hand - ↑ http://www.fasebj.org/cgi/content/meeting_abstract/22/1_MeetingAbstracts/946.11
- ↑ http://www3.interscience.wiley.com/journal/122213505/abstract
- ↑ PMID 15512856 (PMID 15512856)
Citation will be completed automatically in a few minutes. Jump the queue or expand by hand - ↑ Starks MA, Starks SL, Kingsley M, Purpura M, Jäger R (2008). The effects of phosphatidylserine on endocrine response to moderate intensity exercise. J Int Soc Sports Nutr 5: 11.
- ↑ Vitamin C: Stress Buster Psychology today
- ↑ http://news.bbc.co.uk/2/hi/health/5405686.stm
- ↑ http://www.springerlink.com/content/m226111566k24u65/
- ↑ Lovallo WR, Farag NH, Vincent AS, Thomas TL, Wilson MF (March 2006). Cortisol responses to mental stress, exercise, and meals following caffeine intake in men and women. Pharmacol. Biochem. Behav. 83 (3): 441–7.
- ↑ http://cat.inist.fr/?aModele=afficheN&cpsidt=2068517
- ↑ Robson PJ, Blannin AK, Walsh NP, Castell LM, Gleeson M (February 1999). Effects of exercise intensity, duration and recovery on in vitro neutrophil function in male athletes. Int J Sports Med 20 (2): 128–35.
- ↑ PMID 16572599 (PMID 16572599)
Citation will be completed automatically in a few minutes. Jump the queue or expand by hand - ↑ Kraemer WJ, Spiering BA, Volek JS, et al. (January 2009). Recovery from a national collegiate athletic association division I football game: muscle damage and hormonal status. J Strength Cond Res 23 (1): 2–10.
- ↑ PMID 18990498 (PMID 18990498)
Citation will be completed automatically in a few minutes. Jump the queue or expand by hand - ↑ PMID 9181519 (PMID 9181519)
Citation will be completed automatically in a few minutes. Jump the queue or expand by hand - ↑ DOI:10.1016/j.psyneuen.2009.02.015
This citation will be automatically completed in the next few minutes. You can jump the queue or expand by hand - ↑ (2008) Advanced Nutrition and Human Metabolism, 247.
- ↑ http://diabetes.diabetesjournals.org/cgi/content/abstract/58/1/46
- ↑ http://www.ajcn.org/cgi/content/abstract/ajcn.2008.26958v1
- ↑ New Clues about Genetic Influence of Stress on Men’s Health
- ↑ Birth control pills can limit muscle-training gains
- ↑ http://www.utrc2.org/research/assets/74/commuterstress2-report1.pdf
- ↑ includeonly>Iwata, Edward. "Diet pill sellers fined $25M", USA Today, January 5, 2007. Retrieved on 2008-10-26.
- ↑ Mechanism of ACTH action on adrenal cortical cells Andrew N. Margioris, M.D., and Christos Tsatsanis, Ph.D. Updated: December 4, 2006
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