GO:0051413 response to cortisone: Hormone Response Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0051413 (response to cortisone) describes any cellular or organismal change triggered by cortisone, a natural glucocorticoid that is metabolically converted to cortisol.
• Cortisone is synthesized from cholesterol in the adrenal cortex under ACTH stimulation and primarily affects carbohydrate metabolism, including increased hepatic glucose release and glycogen synthesis.
• The response to cortisone involves rapid interconversion between cortisone and cortisol, with the ratio of serum cortisol to cortisone increasing during acute-phase responses.
• Cortisone and its derivatives modulate diverse physiological processes, including growth hormone secretion, erythropoiesis and granulopoiesis, and psychological states.
• Clinically, cortisone responsiveness is relevant to prostate cancer treatment, Addison's disease, and exercise-induced cortisol dynamics.
• Studying response to cortisone requires integrated approaches such as CRISPR knockout/knock-in models, transcriptomics, and targeted hormone assays.
Description
GO:0051413, response to cortisone, is a biological process term that captures the full spectrum of cellular and organismal changes elicited by cortisone, a natural glucocorticoid steroid hormone. Cortisone is synthesized from cholesterol in the adrenal cortex under the stimulation of adrenocorticotropin hormone (ACTH) and is metabolically convertible to cortisol, the primary active glucocorticoid in humans. The main physiological effects of cortisone center on carbohydrate metabolism, where it can stimulate increased glucose release from the liver, enhance liver glycogen synthesis, and decrease glucose utilization by peripheral tissues. This term is essential for researchers because cortisone and its interconversion with cortisol are central to stress responses, metabolic regulation, and immune modulation. For example, the ratio of serum cortisol to cortisone is altered during acute-phase responses, indicating a dynamic regulation of these steroids in systemic inflammation. Moreover, cortisone acetate administration has been shown to acutely affect growth hormone response to growth hormone-releasing hormone in normal adults, linking cortisone to neuroendocrine axes. The response to cortisone also extends to psychological and neurological domains, as early studies documented psychological responses to ACTH, cortisone, and related steroids, and electroencephalographic abnormalities in Addison's disease respond to cortisone replacement. In cancer, the response to aminoglutethimide and cortisone acetate has been evaluated in advanced prostatic cancer, highlighting the therapeutic relevance of modulating cortisone pathways. Additionally, cortisone differentially affects early erythropoietic and granulopoietic progenitors, underscoring its role in hematopoiesis. Understanding GO:0051413 therefore provides a framework for dissecting how a single steroid hormone can orchestrate metabolic, endocrine, immune, and neurological outcomes.
response to cortisone At A Glance
| GO ID | GO:0051413 |
|---|---|
| GO term | response to cortisone |
| Ontology | biological_process |
| Synonym | response to cortisone stimulus |
| Major function | Mediates cellular and systemic changes to cortisone, including metabolic, endocrine, and immune adjustments |
| Definition source | QuickGO |
| Related hormone | Cortisone (convertible to cortisol) |
| Synthesis site | Adrenal cortex, from cholesterol, under ACTH stimulation |
| Primary metabolic effect | Increased hepatic glucose release, increased liver glycogen synthesis, decreased tissue glucose utilization |
What Is GO:0051413?
In our own words, GO:0051413 response to cortisone refers to any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cortisone stimulus. Cortisone is a natural glucocorticoid steroid hormone that is metabolically convertible to cortisol. It is synthesized from cholesterol in the cortex of the adrenal gland under the stimulation of adrenocorticotropin hormone (ACTH). The main physiological effect of cortisone is on carbohydrate metabolism; it can stimulate increased glucose release from the liver, increased liver glycogen synthesis, and decreased utilization of glucose by the tissues. This definition is based on the QuickGO entry for GO:0051413.
Why Is response to cortisone Important in Cell Biology?
The response to cortisone is critically important because cortisone and its active metabolite cortisol are master regulators of carbohydrate metabolism, stress adaptation, and immune function. Dysregulation of this response is implicated in metabolic disorders, inflammatory diseases, and endocrine pathologies. For instance, the serum cortisol to cortisone ratio increases during acute-phase responses, suggesting a role in systemic inflammation. Cortisone acetate affects growth hormone secretion, linking it to growth and neuroendocrine regulation. In oncology, cortisone acetate combined with aminoglutethimide has been used in advanced prostatic cancer, demonstrating therapeutic potential. Furthermore, cortisone influences hematopoiesis by differentially affecting erythroid and granulocytic progenitors, and its absence or excess can lead to neurological and psychological symptoms, as seen in Addison's disease and early psychopharmacology studies. Thus, understanding GO:0051413 is fundamental for developing interventions in metabolic, inflammatory, and neoplastic diseases.
• Cortisone is a key glucocorticoid involved in glucose homeostasis and stress responses.
• The cortisol to cortisone ratio is a biomarker of acute-phase response and inflammation.
• Cortisone modulates growth hormone secretion, impacting growth and metabolism.
• It affects psychological states, with early studies linking cortisone to mood and behavior.
• Cortisone replacement therapy is essential in Addison's disease, where EEG abnormalities improve with treatment.
• Cortisone acetate has been tested in advanced prostate cancer, showing clinical activity.
• It differentially regulates erythropoietic and granulopoietic progenitors, influencing blood cell production.
• Salivary cortisone tracks plasma cortisol response to exercise, offering a non-invasive biomarker.
• Hepatotoxicity studies show that cortisone can modulate drug-induced liver injury.
• Understanding cortisone response pathways can inform therapies for metabolic, inflammatory, and endocrine disorders.
What Happens During response to cortisone?
Cortisone availability and interconversion
In simple terms: Cortisone is a hormone that can be converted into cortisol, the active form, and this balance changes during stress or illness.
The response to cortisone begins with its availability in the circulation. Cortisone is synthesized from cholesterol in the adrenal cortex under ACTH stimulation and is metabolically convertible to cortisol. The ratio of serum cortisol to cortisone is dynamically regulated; during acute-phase responses, this ratio increases, indicating a shift toward cortisol production. This interconversion is mediated by 11beta-hydroxysteroid dehydrogenases (11beta-HSDs), although the specific enzymes are not detailed in the provided citations. The balance between cortisone and cortisol determines the intensity and duration of glucocorticoid signaling.
Neuroendocrine modulation
In simple terms: Cortisone can affect hormone systems, such as growth hormone, by acting on the brain and pituitary.
Cortisone influences neuroendocrine axes. For example, acute administration of cortisone acetate affects growth hormone response to growth hormone-releasing hormone in normal adult subjects, suggesting a modulatory role at the hypothalamic-pituitary level. This indicates that the response to cortisone includes feedback regulation of growth hormone secretion, which can impact growth, metabolism, and stress adaptation. Additionally, psychological responses to cortisone and related steroids have been documented, linking steroid hormones to behavioral and emotional states.
Metabolic effects on carbohydrate metabolism
In simple terms: Cortisone helps raise blood sugar by making the liver release more glucose and store more glycogen, while tissues use less glucose.
The main physiological effect of cortisone is on carbohydrate metabolism. It stimulates increased glucose release from the liver, increased liver glycogen synthesis, and decreased utilization of glucose by tissues. These actions are part of the classic glucocorticoid response and are critical for maintaining blood glucose levels during stress. The QuickGO definition for GO:0051413 explicitly includes these metabolic outcomes. While the provided citations do not directly measure these parameters, the definition is authoritative.
Hematopoietic and immune modulation
In simple terms: Cortisone can change how blood cells are made and how the immune system responds.
Cortisone affects hematopoietic progenitors. Studies show differential responses of early erythropoietic and granulopoietic progenitors to dexamethasone and cortisone, indicating that glucocorticoids can modulate lineage-specific blood cell production. This has implications for immune function and anemia. Additionally, cortisone's role in inflammation is highlighted by the increased cortisol to cortisone ratio in acute-phase responses, suggesting a regulatory loop in systemic inflammation.
Clinical and pharmacological responses
In simple terms: Cortisone is used as a medicine, and its effects are studied in diseases like cancer and Addison's disease.
The response to cortisone is clinically relevant. In advanced prostatic cancer, treatment with aminoglutethimide and cortisone acetate has been evaluated, showing responses that may relate to suppression of adrenal steroidogenesis. In Addison's disease, cortisone replacement reverses electroencephalographic abnormalities, demonstrating its essential role in normal brain function. Furthermore, salivary cortisone tracks plasma cortisol response to exercise, with time-of-day effects, providing a non-invasive measure of adrenal activity. These clinical observations underscore the broad impact of cortisone response pathways.
Key Genes Involved in GO:0051413 response to cortisone
The following genes and proteins are involved in the response to cortisone, based on their roles in glucocorticoid synthesis, metabolism, and signaling as supported by the cited literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| HSD11B1 | Converts cortisone to cortisol | Regulates local glucocorticoid availability; target for metabolic and inflammatory studies |
| HSD11B2 | Converts cortisol to cortisone | Protects mineralocorticoid receptors; involved in hypertension and renal function |
| NR3C1 | Glucocorticoid receptor | Mediates transcriptional effects of cortisol; central to stress and immune responses |
| POMC | Precursor of ACTH | Regulates adrenal steroidogenesis; linked to obesity and pigmentation |
| MC2R | ACTH receptor | Stimulates cortisol synthesis; mutations cause familial glucocorticoid deficiency |
| CYP11B1 | Catalyzes cortisol synthesis | Defects cause congenital adrenal hyperplasia |
| CYP17A1 | Steroidogenesis enzyme | Involved in sex steroid and glucocorticoid production |
| STAR | Cholesterol transport | Rate-limiting for steroidogenesis; mutations cause lipoid CAH |
| CYP21A2 | 21-hydroxylase | Deficiency causes congenital adrenal hyperplasia |
| GHRH | Growth hormone-releasing hormone | Mediates cortisone effects on GH secretion |
| GH1 | Growth hormone | Responds to cortisone acetate |
| EPOR | Erythropoietin receptor | Mediates erythropoietic response to cortisone |
| CSF2 | GM-CSF | Influences granulopoietic response to cortisone |
| IL6 | Interleukin-6 | Acute-phase response linked to cortisol/cortisone ratio |
| TNF | Tumor necrosis factor | Inflammatory mediator modulated by glucocorticoids |
| NR3C2 | Mineralocorticoid receptor | Affected by cortisol/cortisone balance |
| SLC2A4 | GLUT4 glucose transporter | Mediates glucose uptake changes in response to glucocorticoids |
| PCK1 | Phosphoenolpyruvate carboxykinase | Key enzyme in gluconeogenesis stimulated by cortisone |
How Is response to cortisone Regulated?
The response to cortisone is regulated at multiple levels. The interconversion between cortisone and cortisol is controlled by 11beta-hydroxysteroid dehydrogenase enzymes, which are expressed in a tissue-specific manner. The ratio of serum cortisol to cortisone increases during acute-phase responses, indicating that inflammation can shift this balance. Neuroendocrine regulation involves ACTH from the pituitary, which stimulates adrenal steroidogenesis. Additionally, cortisone acetate can acutely modulate growth hormone response to GHRH, suggesting feedback regulation within the hypothalamic-pituitary-adrenal axis. Psychological and neurological responses to cortisone also imply central regulatory mechanisms. The differential effects on hematopoietic progenitors further indicate that the response is context-dependent and cell-type specific.
response to cortisone and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| HSD11B1 | Metabolic syndrome, inflammation | Knockout mouse, overexpression cell line |
| NR3C1 | Glucocorticoid resistance, depression | Point mutation knock-in mouse |
| CYP21A2 | Congenital adrenal hyperplasia | Patient-derived iPSCs, knock-in |
| POMC | Obesity, adrenal insufficiency | Knockout mouse, CRISPR KO cell line |
| IL6 | Acute-phase response, inflammation | Overexpression cell line, KO mouse |
Metabolic and endocrine disorders
Dysregulation of cortisone and cortisol balance is implicated in metabolic syndrome, obesity, and type 2 diabetes. The cortisol to cortisone ratio is altered in acute-phase responses, which may contribute to insulin resistance and hyperglycemia. In Addison's disease, lack of cortisol leads to EEG abnormalities that are reversed by cortisone replacement, highlighting the importance of glucocorticoid signaling in neurological function. Congenital adrenal hyperplasia and familial glucocorticoid deficiency are caused by mutations in genes involved in cortisol synthesis, such as CYP21A2 and MC2R, though these are not directly cited in the provided references.
Cancer
Cortisone and its derivatives are used in cancer therapy. In advanced prostatic cancer, the combination of aminoglutethimide and cortisone acetate has shown clinical responses, likely through suppression of adrenal androgen production. Glucocorticoids are also used to manage side effects of chemotherapy and to treat hematological malignancies, although the specific mechanisms are not detailed in the cited papers.
Inflammatory and immune disorders
The acute-phase response involves a shift in cortisol/cortisone ratio, suggesting that cortisone metabolism is part of the systemic inflammatory response. Glucocorticoids are potent anti-inflammatory agents, and their effects on immune cells are well known. The differential response of hematopoietic progenitors to cortisone may contribute to immune modulation and anemia of inflammation.
Neurological and psychological conditions
Early studies documented psychological responses to cortisone and related steroids, including mood changes and psychotic symptoms. In Addison's disease, cortisone replacement improves EEG abnormalities, indicating a role for glucocorticoids in brain function. These findings link cortisone response to neuropsychiatric disorders, although the underlying mechanisms require further research.
From response to cortisone-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X mediate cortisone-induced glucose release? | CRISPR knockout hepatocyte cell line |
| How does a point mutation in HSD11B1 affect cortisone conversion? | Point mutation knock-in cell model |
| Can overexpression of NR3C1 enhance cortisone sensitivity? | Overexpression stable cell line |
| What is the role of gene Y in cortisone-induced hematopoietic changes? | Tagged knock-in mouse for lineage tracing |
| Which genes are essential for cortisone response in immune cells? | CRISPR library screening in macrophage cell line |
| Does a disease-associated SNP in gene Z alter cortisone response? | Knock-in of SNP using CRISPR |
How to Study the response to cortisone Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Global gene expression changes | Identify cortisone-responsive genes |
| Salivary cortisol/cortisone assay | Hormone levels and ratio | Non-invasive monitoring of adrenal response |
| CRISPR knockout screen | Gene essentiality for cortisone response | Discover novel regulators |
| Western blot | Protein expression and phosphorylation | Validate signaling pathways |
| Metabolomics | Metabolite changes (glucose, glycogen) | Assess metabolic effects |
| EEG | Brain electrical activity | Evaluate neurological response in Addison's disease |
| Growth hormone stimulation test | GH secretion | Assess neuroendocrine effects of cortisone |
Transcriptomic profiling
RNA sequencing (RNA-seq) can identify global gene expression changes in response to cortisone. This method is useful for discovering novel cortisone-responsive genes and pathways. For example, comparing treated and untreated cells can reveal upregulation of gluconeogenic enzymes like PCK1. The cited literature does not include RNA-seq studies, but the approach is standard in the field.
Hormone quantification
Measuring cortisol and cortisone levels in serum or saliva is essential to assess the response. The ratio of cortisol to cortisone is a key biomarker, as shown in acute-phase responses. Salivary cortisone tracks plasma cortisol response to exercise, offering a non-invasive method. These assays can be used in clinical and preclinical studies.
CRISPR-based genetic screens
Pooled CRISPR knockout or activation screens can identify genes that modulate cortisone response. For instance, screening for resistance or hypersensitivity to cortisone-induced growth arrest can uncover novel regulators. This approach is powerful for unbiased discovery and can be combined with RNA-seq readouts.
Proteomics and metabolomics
Mass spectrometry-based proteomics and metabolomics can quantify changes in protein abundance and metabolite levels following cortisone treatment. These methods can validate metabolic effects such as increased glycogen synthesis and glucose release. While not cited here, they are complementary to genetic approaches.
How CRISPR Can Be Used to Study GO:0051413 response to cortisone
Knockout
CRISPR knockout (KO) of candidate genes such as HSD11B1 or NR3C1 can determine their necessity for cortisone response. For example, KO of HSD11B1 would prevent conversion of cortisone to cortisol, abolishing downstream effects. This approach is ideal for validating gene function in cell models.
Point Mutation
Introducing precise point mutations via CRISPR can model disease-associated variants or dissect functional domains. For instance, a point mutation in NR3C1 that affects ligand binding can be knocked into cells to study altered cortisone sensitivity. This is valuable for understanding genetic contributions to glucocorticoid resistance.
Knock-in
Knock-in of reporter tags (e.g., GFP) or epitope tags allows visualization and purification of proteins involved in cortisone response. Tagging endogenous HSD11B1 can reveal its localization and dynamics upon cortisone stimulation. Knock-in of entire genes or regulatory elements can also be used to study expression control.
Overexpression
Overexpression of genes like NR3C1 or HSD11B1 using CRISPR activation (CRISPRa) or lentiviral vectors can enhance cortisone response. This is useful for gain-of-function studies and for producing cell models with heightened sensitivity to glucocorticoids. Overexpression can also rescue phenotypes in KO backgrounds.
How EDITGENE Supports response to cortisone Research
Researchers studying response to cortisone-related genes often need to determine whether a candidate gene is causally involved in mediating the effects of cortisone or its metabolite cortisol. This requires precise genetic manipulation, which can be achieved through CRISPR-based knockout, point mutation, knock-in, or overexpression models. EDITGENE provides end-to-end services to generate such models and to screen for genes that modulate cortisone response.
Contact EDITGENE today to design your custom CRISPR model for response to cortisone research.
Frequently Asked Questions About response to cortisone
What is GO:0051413 response to cortisone?
GO:0051413 is a Gene Ontology biological process term that describes any process resulting in a change in cell or organism state or activity due to a cortisone stimulus. Cortisone is a glucocorticoid hormone convertible to cortisol, primarily affecting carbohydrate metabolism.
What genes are involved in response to cortisone?
Key genes include HSD11B1, HSD11B2, NR3C1, POMC, MC2R, CYP11B1, CYP17A1, STAR, and CYP21A2, among others. These genes regulate cortisone synthesis, interconversion, and signaling.
How does cortisone affect carbohydrate metabolism?
Cortisone stimulates increased glucose release from the liver, increased liver glycogen synthesis, and decreased utilization of glucose by tissues, as defined in GO:0051413.
What is the difference between cortisone and cortisol?
Cortisone is a natural glucocorticoid that is metabolically convertible to cortisol, the primary active glucocorticoid in humans. The interconversion is mediated by 11beta-hydroxysteroid dehydrogenases.
Why is the cortisol to cortisone ratio important?
The ratio of serum cortisol to cortisone increases during acute-phase responses, indicating a shift in steroid metabolism during inflammation.
How is response to cortisone studied in the lab?
Researchers use hormone assays, RNA-seq, CRISPR knockout/knock-in models, and proteomics to study the molecular and physiological changes induced by cortisone.
What diseases are associated with abnormal cortisone response?
Diseases include Addison's disease, metabolic syndrome, prostate cancer, and inflammatory conditions. Cortisone replacement reverses EEG abnormalities in Addison's disease.
Can cortisone affect growth hormone secretion?
Yes, acute cortisone acetate administration affects growth hormone response to growth hormone-releasing hormone in normal adults.
Does cortisone influence blood cell production?
Cortisone differentially affects early erythropoietic and granulopoietic progenitors, indicating a role in hematopoiesis.
How can CRISPR help study response to cortisone?
CRISPR knockout, point mutation, knock-in, and overexpression models allow precise manipulation of genes like HSD11B1 and NR3C1 to determine their causal roles in cortisone response.
Conclusion
GO:0051413 response to cortisone is a fundamental biological process that integrates metabolic, endocrine, immune, and neurological signals. The interconversion between cortisone and cortisol, along with tissue-specific responses, underscores the complexity of glucocorticoid biology. Understanding this process has clinical implications for diseases ranging from Addison's disease to prostate cancer. Leveraging CRISPR-based models and multi-omics approaches will continue to unravel the mechanisms and identify therapeutic targets.
References
- 1. Vogeser M et al.. 2002. Increased ratio of serum cortisol to cortisone in acute-phase response.. Horm Res 58(4):172-5 PMID: 12324714
- 2. Ponder BA et al.. 1984. Response to aminoglutethimide and cortisone acetate in advanced prostatic cancer.. Br J Cancer 50(6):757-63 PMID: 6238616
- 3. ROME HP et al.. 1952. The psychological response to ACTH, cortisone, hydrocortisone, and related steroid substances.. Am J Psychiatry 108(9):641-51 PMID: 14903192
- 4. ELLIOTT HW et al.. 1955. Hepatotoxicity of chlorpromazine and its response to cortisone.. Stanford Med Bull 13(4):536-40 PMID: 13274243
- 5. Giustina A et al.. 1990. Acute effects of cortisone acetate on growth hormone response to growth hormone-releasing hormone in normal adult subjects.. Acta Endocrinol (Copenh) 122(2):206-10 PMID: 2107653
- 6. Del Corral P et al.. 2016. Salivary but not plasma cortisone tracks the plasma cortisol response to exercise: effect of time of day.. J Endocrinol Invest 39(3):315-22 PMID: 26243508
- 7. SKANSE B et al.. 1958. Electroencephalographic abnormalities in Addison's disease and its response to cortisone.. Acta Endocrinol (Copenh) 27(4):469-81 PMID: 13532365
- 8. Zalman F et al.. 1979. Differential response of early erythropoietic and granulopoietic progenitors to dexamethasone and cortisone.. J Exp Med 149(1):67-72 PMID: 762496
