Page last updated: 2024-10-24

negative regulation of cortisol secretion

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of the regulated release of cortisol from a cell. [GOC:ai]

Negative regulation of cortisol secretion is a complex process involving a series of feedback loops and signaling pathways that ultimately reduce the production and release of cortisol from the adrenal glands. This process is crucial for maintaining homeostasis and preventing excessive stress responses.

**Hypothalamic-Pituitary-Adrenal (HPA) Axis:**

The HPA axis is the primary regulatory system for cortisol secretion. The hypothalamus, located in the brain, releases corticotropin-releasing hormone (CRH) in response to stress signals. CRH stimulates the anterior pituitary gland to produce adrenocorticotropic hormone (ACTH). ACTH then travels through the bloodstream to the adrenal glands, specifically the adrenal cortex, where it triggers the synthesis and release of cortisol.

**Negative Feedback Loops:**

Cortisol itself plays a key role in regulating its own production through negative feedback loops.

* **Hypothalamic Feedback:** Cortisol binds to glucocorticoid receptors (GRs) in the hypothalamus, inhibiting the release of CRH, thus reducing ACTH production.
* **Pituitary Feedback:** Cortisol also binds to GRs in the pituitary gland, directly suppressing ACTH release.

**Other Regulatory Mechanisms:**

* **Neural Input:** The HPA axis can be influenced by various neural inputs, including signals from the amygdala (involved in fear and anxiety) and the hippocampus (involved in memory and learning). These inputs can modulate CRH release and subsequent cortisol secretion.
* **Circadian Rhythm:** Cortisol secretion follows a circadian rhythm, with peak levels occurring in the early morning and lower levels in the evening. This rhythm is regulated by the suprachiasmatic nucleus (SCN) in the hypothalamus, which acts as the body's internal clock.
* **Other Hormones:** Hormones like dopamine, serotonin, and norepinephrine can also influence cortisol release. For instance, dopamine can suppress ACTH release, while norepinephrine can stimulate it.

**Consequences of Dysregulation:**

Imbalances in the negative regulation of cortisol secretion can lead to various health problems, including:

* **Chronic Stress and Anxiety:** When cortisol levels are chronically elevated, it can contribute to stress, anxiety, and mood disorders.
* **Metabolic Disturbances:** Prolonged cortisol elevation can cause insulin resistance, leading to metabolic syndrome and increased risk of type 2 diabetes.
* **Immune Suppression:** Cortisol can suppress immune function, making the body more vulnerable to infections.
* **Cardiovascular Disease:** High cortisol levels are associated with increased risk of cardiovascular diseases, including hypertension and heart disease.

In summary, negative regulation of cortisol secretion is a vital process for maintaining homeostasis and mitigating the negative effects of prolonged stress. It involves complex feedback loops and signaling pathways that ensure appropriate cortisol levels are maintained within the body.'
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Proteins (1)

ProteinDefinitionTaxonomy
Tyrosine-protein phosphatase non-receptor type 11A tyrosine-protein phosphatase non-receptor type 11 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q06124]Homo sapiens (human)

Compounds (24)

CompoundDefinitionClassesRoles
glycyrrhetinic acidcyclic terpene ketone;
hydroxy monocarboxylic acid;
pentacyclic triterpenoid
immunomodulator;
plant metabolite
oxanilic acidoxanilic acid: RN given refers to parent cpd; structure
oleanolic acidhydroxy monocarboxylic acid;
pentacyclic triterpenoid
plant metabolite
phosphotyrosineO(4)-phospho-L-tyrosine : A non-proteinogenic L-alpha-amino acid that is L-tyrosine phosphorylated at the phenolic hydroxy group.

Phosphotyrosine: An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.
L-tyrosine derivative;
non-proteinogenic L-alpha-amino acid;
O(4)-phosphotyrosine
Escherichia coli metabolite;
immunogen
vanadatesvanadate(3-) : A vanadium oxoanion that is a trianion with formula VO4 in which the vanadium is in the +5 oxidation state and is attached to four oxygen atoms.

Vanadates: Oxyvanadium ions in various states of oxidation. They act primarily as ion transport inhibitors due to their inhibition of Na(+)-, K(+)-, and Ca(+)-ATPase transport systems. They also have insulin-like action, positive inotropic action on cardiac ventricular muscle, and other metabolic effects.
trivalent inorganic anion;
vanadium oxoanion
EC 3.1.3.1 (alkaline phosphatase) inhibitor;
EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor;
EC 3.1.3.41 (4-nitrophenylphosphatase) inhibitor;
EC 3.1.3.48 (protein-tyrosine-phosphatase) inhibitor
4-methylumbelliferyl phosphate
maslinic acid(2Alpha,3beta)-2,3-dihydroxyolean-12-en-28-oic acid: from Luehea divaricata and Agrimonia eupatoriadihydroxy monocarboxylic acid;
pentacyclic triterpenoid
anti-inflammatory agent;
antineoplastic agent;
antioxidant;
plant metabolite
nsc-87877NSC-87877: potent Shp2 (nonreceptor protein tyrosine phosphatase) inhibitor; structure in first source
tingenonetingenone: quinonoid triterpene isolated from Euonymus tingens
geniposideterpene glycoside
tanshinonetanshinone: from root of Salvia miltiorrhiza Bunge; RN given refers to tanshinone I; cardioprotective agent and neuroprotective agentabietane diterpenoidanticoronaviral agent
celastrolmonocarboxylic acid;
pentacyclic triterpenoid
anti-inflammatory drug;
antineoplastic agent;
antioxidant;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
Hsp90 inhibitor;
metabolite
cryptotanshinonecryptotanshinone: from Salvia miltiorrhizaabietane diterpenoidanticoronaviral agent
tanshinone ii atashinone IIA: a cardiovascular agent with antineoplastic activity; isolated from Salvia miltiorrhiza; structure in first sourceabietane diterpenoid
nsc-89199estramustine phosphate : A steroid phosphate which is the 17-O-phospho derivative of estramustine.carbamate ester;
organochlorine compound;
steroid phosphate
estramustineestramustine : A carbamate ester obtained by the formal condensation of the hydroxy group of 17beta-estradiol with the carboxy group of bis(2-chloroethyl)carbamic acid.

Estramustine: A nitrogen mustard linked to estradiol, usually as phosphate; used to treat prostatic neoplasms; also has radiation protective properties.
17beta-hydroxy steroid;
carbamate ester;
organochlorine compound
alkylating agent;
antineoplastic agent;
radiation protective agent
genipiniridoid monoterpenoidanti-inflammatory agent;
antioxidant;
apoptosis inhibitor;
cross-linking reagent;
hepatotoxic agent;
uncoupling protein inhibitor
cefsulodincefsulodin : A pyridinium-substituted semi-synthetic, broad-spectrum, cephalosporin antibiotic.

Cefsulodin: A pyridinium-substituted semisynthetic, broad-spectrum antibacterial used especially for Pseudomonas infections in debilitated patients.
cephalosporin;
organosulfonic acid;
primary carboxamide
antibacterial drug
nsc 117199
illudalic acidilludalic acid: isolated from Clitocybe illudens; structure in first source
2-amino-6-chloropurine6-chloroguanine : An organochlorine compound that is 7H-purin-2-amine substituted by a chloro group at position 6.

6-chloroguanine: an antimalarial that inhibits hypoxanthine-guanine-xanthine phosphoribosyltransferase; structure in first source
2-aminopurines;
organochlorine compound
4-(3-(1-adamantyl)-4-hydroxyphenyl)-3-chlorocinnamic acid
Dihydrotanshinone Idihydrotanshinone I: extracted from Radix Salviaeabietane diterpenoidanticoronaviral agent
3-(1-(3-(biphenyl-4-ylamino)-3-oxopropyl)-1h-1,2,3-triazol-4-yl)-6-hydroxy-1-methyl-2-phenyl-1h-indole-5-carboxylic acid3-(1-(3-(biphenyl-4-ylamino)-3-oxopropyl)-1H-1,2,3-triazol-4-yl)-6-hydroxy-1-methyl-2-phenyl-1H-indole-5-carboxylic acid: an SHP2 inhibitor; structure in first source