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Event: 2371

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Increased cortisol

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Increased cortisol
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Cellular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Cell term
eukaryotic cell

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Organ term
central nervous system

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
peptide biosynthetic process increased
receptor binding occurrence

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
Binding of Alpha 1-Adrenergics to Antagonists Leading to Depression KeyEvent LUANA GOMES (send email) Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
mammals mammals High NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
All life stages High

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Unspecific High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help
  • Cortisol is widely known as the stress hormone, but it also performs several other functions in the body. It is the primary glucocorticoid released by the zona fasciculata of the adrenal cortex. Its production is initiated by activation of the hypothalamic–pituitary–adrenal (HPA) axis, which regulates both the synthesis and secretion of the hormone. (Thau Et Al; 2023)
  • ACTH is responsible for stimulating cortisol production by regulating the various steps of the steroidogenic pathway. This includes: 1) increasing the number of low-density lipoprotein (LDL) receptors; 2) cleavage of the cholesterol side chain to convert it into pregnenolone, which represents the first step and the rate-limiting stage of cortisol production. ( Angelousi Et Al; 2000) 
  • Glucocorticoid receptors are present in various tissues throughout the body and can influence multiple organ systems, including the nervous, immune, reproductive, gastrointestinal, musculoskeletal, integumentary, and cardiovascular systems. (Kadmiel Et Al; 2013) 
  •  Their synthesis and release are dynamically regulated by the hypothalamic–pituitary–adrenal (HPA) axis, following both circadian and ultradian rhythms. (Biddie Et Al; 2012)
  • Glucocorticoid availability is regulated by corticosteroid-binding globulin and 11β-hydroxysteroid dehydrogenase (11β-HSD) enzymes, which are locally expressed in tissues. (Clark Et Al; 2012)
  • If excessive stimulation of cortisol production occurs, the physiological and homeostatic levels of serum cortisol will be disrupted, leading to impaired health and the development of diseases such as diabetes and depression. (Norris Et Al; 2020) 

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help
  • Cortisol can be measured in serum and plasma. (World Health Organization; 2017) 
  • The earliest techniques for measuring cortisol involved fluorimetric analysis experiments. (Campuzano Et Al; 1973)
  • Cortisol levels can be assessed in various biological fluids, including serum, urine, and saliva. Serum cortisol assays measure total cortisol but can be influenced by changes in serum protein concentrations. Automated immunoassays are widely used, although they have limitations in specificity and show significant inter-assay variability. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) provides greater specificity and sensitivity and is recommended for salivary and urinary cortisol measurements. Twenty-four-hour urinary free cortisol is a reliable indicator of serum free cortisol and is useful for monitoring Cushing's syndrome. Salivary cortisol reflects changes in serum free cortisol and offers a non-invasive alternative, although reference ranges have not yet been standardized. (El-Farhan Et Al; 2017) 
  • The gold standard for detecting free serum cortisol is mass spectrometry, a technique employed for molecular characterization and also used to quantify free cortisol levels. (Masjkur Et Al; 2019) 

  • Immunoassays for cortisol quantification can employ monoclonal antibodies, aptamers, or molecularly imprinted polymers as bioreceptors. (Yulianti Et Al; 2022)

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help
  • This Key Event is applicable to mammals, birds, and rodents. In mammals, the main glucocorticoids involved in the stress response are cortisol and cortisone, whereas in birds and rodents, the primary glucocorticoid is corticosterone (Botía et al., 2020).
  • Other studies have also investigated the elevation of cortisol in different animal species. For instance, in a study conducted on rainbow trout (Oncorhynchus mykiss) reared in captivity, cortisol levels were measured after the fish were suspended in air as a stressor. The results showed that this stressor led to an increase in cortisol concentrations both in plasma and in the surrounding water, confirming that the stress response is conserved across species. (Wiseman et al., 2011). 
  • Cortisol and corticosterone levels have also been assessed in sheep hair following bacterial inoculation in the right foot, used as a model of chronic stress. Overall, cortisone concentrations in hair were higher than cortisol levels. Furthermore, cortisone levels increased significantly two weeks after inoculation, whereas cortisol levels decreased relative to baseline values. According to the authors, these findings may be attributed to an enhanced local activity of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) as a consequence of chronic stress. (Stubsjøen et al., 2015). 

References

List of the literature that was cited for this KE description. More help
  1. Thau, L. (2023). Physiology, Cortisol. StatPearls. Disponível em: https://www.ncbi.nlm.nih.gov/books/NBK538239/
  2. Sheng, J.A. (2021). The Hypothalamic–Pituitary–Adrenal Axis. PubMed Central. Disponível em: https://pmc.ncbi.nlm.nih.gov/articles/PMC7838595/
  3. Herman, J.P. (2016). Regulation of the Hypothalamic-Pituitary-Adrenocortical Stress Response. PubMed Central. Disponível em: https://pmc.ncbi.nlm.nih.gov/articles/PMC4867107/
  4. Kater, C.E. (2022). Classic and Current Concepts in Adrenal Steroidogenesis. PubMed Central. Disponível em: https://pmc.ncbi.nlm.nih.gov/articles/PMC9991025/
  5. Arlt, W. (2005). Adrenal Corticosteroid Biosynthesis, Metabolism, and Action. PubMed. Disponível em: https://pubmed.ncbi.nlm.nih.gov/15850843/
  6. Cortisol - an overview. ScienceDirect Topics. Disponível em: https://www.sciencedirect.com/topics/neuroscience/cortisol
  7. Schiffer, L. (2019). Human Steroid Biosynthesis, Metabolism and Excretion. PubMed Central. Disponível em: https://pmc.ncbi.nlm.nih.gov/articles/PMC6857441/
  8. World Health Organization (WHO). 2002. Use of anticoagulants in laboratory diagnostic investigations (WHO/DIL/LAB/99.1 Rev.2). Available at: http://apps.who.int/iris/bitstream/10665/65957/1/WHO_DIL_LAB_99.1_REV.2.pdf. 

  9. El-Farhan, N., Rees, D. A. & Evans, C. 2017. Measuring cortisol in serum, urine and saliva – are our assays good enough? Annals of Clinical Biochemistry, 54(3), 308–322. DOI: 10.1177/0004563216687335. 

  10. Harrison, J. M., & McEwen, B. S. 1973. Measurement of cortisol in biological fluids. Journal of Clinical Endocrinology & Metabolism, 36(6), 1189–1195. DOI: 10.1210/jcem-36-6-1189. 

  11. Norris, D. O., & Carr, J. A. 2019. Vertebrate Endocrinology. 5ª ed. Academic Press. ISBN: 978-0128149221. 

  12. Masjkur, J., Gruber, M., Peitzsch, M., Kaden, D., Di Dalmazi, G., Bidlingmaier, M., Zopp, S., Langton, K., Fazel, J., Beuschlein, F., Bornstein, S. R., Reincke, M., & Eisenhofer, G. 2019. Plasma steroid profiles in subclinical compared with overt adrenal Cushing syndrome. Journal of Clinical Endocrinology & Metabolism, 104(10), 4331–4340. DOI: 10.1210/jc.2018-02349. PMID: 30977834. 

  13.  Yulianti, E. S., Rahman, S. F., & Whulanza, Y. 2022. Molecularly imprinted polymer-based sensor for electrochemical detection of cortisol. Biosensors, 12(12), 1090. DOI: 10.3390/bios12121090. 

  14. Botía, M., Escribano, D., Martínez-Subiela, S., Tvarijonaviciute, A., Tecles, F., López-Arjona, M., & Cerón, J. J. (2020). Different types of glucocorticoids to assess stress and welfare in animals and humans: General concepts and examples of use in combination. General and Comparative Endocrinology, 295, 113545. https://doi.org/10.1016/j.ygcen.2020.113545 

  15. Wiseman, S., Thomas, J. K., McPhee, L., Hursky, O., Raine, J. C., Pietrock, M., Giesy, J. P., Hecker, M., & Janz, D. M. (2011). Attenuation of the cortisol response to stress in female rainbow trout chronically exposed to dietary selenomethionine. Aquatic Toxicology, 105(3–4), 643–651. https://doi.org/10.1016/j.aquatox.2011.09.002 

  16. Stubsjøen, S. M., Bohlin, J., Dahl, E., Knappe-Poindecker, M., Fjeldaas, T., Lepschy, M., Palme, R., Langbein, J., & Ropstad, E. (2015). Assessment of chronic stress in sheep (Part I): The use of cortisol and cortisone in hair as non-invasive biological markers. Small Ruminant Research, 132, 25–31. https://doi.org/10.1016/j.smallrumres.2015.09.015