Glucocorticoids: Types, Functions, and Health Impacts

Glucocorticoids (or, less generally, glucocorticosteroids) are a type of steroid hormone that belongs to the corticosteroids family. Glucocorticoids are corticosteroids which bind with the glucocorticoid receptor, which is found in nearly each cell of a vertebrate animal. The term "glucocorticoid" is a shortened version of "glucose + cortex + steroid," and refers to its function in glucose metabolism, adrenal cortex synthesis, and steroidal structure.

Glucocorticoids are a component of the immune system's feedback process that helps to minimise inflammation and other forms of immune function. As a result, they're used to treat illnesses like asthma, allergies, sepsis and autoimmune diseases that are exacerbated via an overactive immune system. Since glucocorticoids provide a wide range of (pleiotropic) effects, such as potentially bad side effects, they are seldom available over-the-counter. They often disrupt a few of the abnormal pathways in cancer cells, so they're able to precisely treat cancer at high doses.

Through binding with the glucocorticoid receptor, glucocorticoids have an effect on cells. By blocking the translocation of several other transcription factors from the cytosol further into the nucleus, the triggered glucocorticoid receptor-glucocorticoid complex up-regulates the expression of anti-inflammatory proteins in the nucleus and inhibits the expression of proinflammatory proteins in the cytosol (transrepression).

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Types of Glucocorticoids

Below stated are the major types of glucocorticoids:-

• Cortisone is a shot that can help with joint inflammation.

• Prednisone and dexamethasone are glucocorticosteroids that are used to treat allergies, arthritis, asthma, vision disorders, and a variety of other ailments.

• Triamcinolone is a topical cream that is used to treat skin disorders.

• Budesonide is a medication used to treat ulcerative colitis and Crohn's disease, both of which are inflammatory conditions that affect the digestive tract.

Few Others are:-

• Inhaled Corticosteroids:- Medicines containing corticosteroids including budesonide, ciclesonide, beclomethasone, flunisolide, mometasone or fluticasone in a preparation intended to have been inhaled via the mouth are known as inhaled corticosteroids. Inhaled corticosteroids suppress the inflammatory process which triggers asthma by acting directly in the lungs.

• Topical Glucocorticoids:- Skin disorders such as rash, dermatitis, itching, eczema, and psoriasis are treated with topical corticosteroids, which are synthetic (man-made) corticosteroids. Topical corticosteroids provide potent anti-inflammatory properties as well as the ability to suppress the immune system. Topical corticosteroids are prescribed based on their efficacy, the body region to which they would be administered, and the type of skin disorder being treated.

• Dexamethasone Glucocorticoid: Dexamethasone is an anti-inflammatory and immunosuppressive synthetic glucocorticoid. Dexamethasone seems to be an effective treatment for PONV and CINV since it possesses 20 to 30 times the binding affinity for glucocorticoid receptors in the form of endogenous cortisol. Despite the fact that dexamethasone is one of the most widely prescribed antiemetics, its mechanism of action is unknown.

• Systemic Glucocorticoids: A systemic steroid is a corticosteroid that is taken orally or administered intramuscularly. Systemic steroids constitute synthetic derivatives of cortisol, a natural steroid released via the adrenal glands that have potent anti-inflammatory properties.

Effects

The effects of glucocorticoid steroids can be divided into two categories: immunological and metabolic. Glucocorticoids are also essential for foetal development as well as homeostasis of body fluid.

Immune: 

Glucocorticoids cortisol work by interacting with the glucocorticoid receptor, as explained further below:

• Anti-inflammatory proteins' expression tends to be increased.

• suppression of  the expression of proinflammatory proteins

T lymphocyte formation and homeostasis have also been shown to be influenced by glucocorticoids. It has been demonstrated in transgenic mice through increased or decreased glucocorticoid sensitivity of the T cell lineage.

Metabolic:

The term "glucocorticoid" comes from the fact that such hormones had been discovered to be engaged in glucose metabolism. Cortisol activates many mechanisms in the fasted state that work together to increase and sustain regular glucose levels in the blood.

Impact on Metabolism:

• Stimulation of gluconeogenesis, specifically in the liver: Such process leads in the production of glucose from non-hexose substrates like glycerol and amino acids from triglyceride breakdown, and seems to be especially essential in carnivores and some herbivores.

• Amino acids from extrahepatic tissues are mobilised and used as gluconeogenesis substrates.

• A mechanism to store glucose is the inhibition of glucose absorption in muscle and adipose tissue.

• Lipolysis releases fatty acids, which are utilized for the energy production in tissues including muscle, and the produced glycerol provides another substrate towards gluconeogenesis.

• Hypernatremia and hypokalemia are caused by the rise in potassium excretion.

Developmental: Glucocorticoids affect foetal development in a variety of ways. Their purpose is to promote lung maturation and the development of the surfactant required for extrauterine lung function is an amazing illustration. Mice containing homozygous disruptions in the corticotropin-releasing hormone gene die of pulmonary immaturity before reaching adulthood. Furthermore, glucocorticoids are required for normal and proper brain development because they initiate remodel axons, terminal maturation, and dendrites, as well as influence cell survival, and they may also contribute to hippocampal development. 

Arousal and Cognition: The amygdala, hippocampus, and frontal lobes are all affected by glucocorticoids. This facilitates the production of flashbulb memories of factors linked with intense feelings, both positive and negative, in addition to adrenaline. It has been proven in research where glucocorticoid or noradrenaline blockade reduced the memory of emotionally significant details. According to other sources, individuals whose fear of learning has been followed by elevated cortisol levels had improved memory consolidation. The memory-improving effects of glucocorticoids could be the result of damage to the hippocampal formation's CA1 region. Prolonged stress (leading to prolonged rises in glucocorticoid levels) has indeed been linked to the loss of neurons in this region of the brain in several animal studies, that has been linked to poor memory output.

Body Fluid Homeostasis: By controlling the body's response to atrial natriuretic peptide, glucocorticoids can help to normalise extracellular fluid volume both centrally and peripherally (ANP). Glucocorticoids may suppress dehydration-induced water intake centrally while also causing a potent diuresis peripherally.

Mineralocorticoids

Mineralocorticoids are a subclass of corticosteroids, that are steroid hormones in and of themselves. Mineralocorticoids are hormones that are formed in the adrenal cortex and have an effect on salt and water balance (fluid balance and electrolyte balance). Aldosterone is the most important mineralocorticoid.

The term mineralocorticoid comes through early findings that these hormones play a role in the mineral sodium retention. Aldosterone is the main endogenous mineralocorticoid, though some endogenous hormones (such as deoxycorticosterone and progesterone) also have mineralocorticoid roles. Aldosterone works on the kidneys in order to provide active sodium reabsorption and passive water reabsorption, and also active potassium secretion there in cortical collecting tubule's principal cells and active protons secretion through proton ATPases with in lumenal membrane of that of the intercalated collecting tubule's intercalated cells. Due to this, there is a rise in blood volume and Blood pressure.

Aldosterone is formed in the zona glomerulosa of the adrenal cortex, where it is secreted primarily by angiotensin II, but also through adrenocorticotropic hormone (ACTH) and specific potassium levels.

Glucocorticoid Remediable Aldosteronism

Aldosterone synthase hyperactivity, also known as glucocorticoid remediable aldosteronism, is an autosomal dominant condition wherein the rise in aldosterone secretion caused by ACTH seems to be no longer temporary. This can lead to Primary hyperaldosteronism

Sufferers with GRA could be symptom free, but they may experience the following symptoms:

• Fatigue

• Hypokalemia

• High blood pressure

• Muscle spasms

• Headache

• Intermittent or temporary paralysis

• Muscle weakness

• Numbness

• Muscle spasms

• Polydipsia

• Polyuria