Extra-adrenal glucocorticoid biosynthesis: implications for autoimmune and inflammatory disorders.

Extra-adrenal glucocorticoid biosynthesis: implications for autoimmune and inflammatory disorders.

Publication date: Mar 23, 2020

Glucocorticoid synthesis is a complex, multistep process that starts with cholesterol being delivered to the inner membrane of mitochondria by StAR and StAR-related proteins. Here its side chain is cleaved by CYP11A1 producing pregnenolone. Pregnenolone is converted to cortisol by the enzymes 3-?HSD, CYP17A1, CYP21A2, and CYP11B1. Glucocorticoids play a critical role in the regulation of the immune system and exert their action through the glucocorticoid receptor (GR). Although corticosteroids are primarily produced in the adrenal gland, they can also be produced in a number of extra-adrenal tissue including the immune system, skin, brain, and intestine. Glucocorticoid production is regulated by ACTH, CRH, and cytokines such as IL-1, IL-6, and TNF?. The bioavailability of cortisol is also dependent on its interconversion to cortisone, which is inactive, by 11?HSD1/2. Local and systemic glucocorticoid biosynthesis can be stimulated by ultraviolet B, explaining its immunosuppressive activity. In this review, we want to emphasize that dysregulation of extra-adrenal glucocorticoid production can play a key role in a variety of autoimmune diseases including multiple sclerosis (MS), lupus erythematosus (LE), rheumatoid arthritis (RA), and skin inflammatory disorders such as psoriasis and atopic dermatitis (AD). Further research on local glucocorticoid production and its bioavailability may open doors into new therapies for autoimmune diseases.

Slominski, R.M., Tuckey, R.C., Manna, P.R., Jetten, A.M., Postlethwaite, A., Raman, C., and Slominski, A.T. Extra-adrenal glucocorticoid biosynthesis: implications for autoimmune and inflammatory disorders. 20514. 2020 Genes Immun.

Concepts Keywords
ACTH Autoimmune diseases
Adrenal Steroids
Adrenal Gland Branches of biology
Atopic Dermatitis Corticosteroids
Autoimmune Pregnanes
Autoimmune Diseases Endocrine system
Bioavailability Steroid hormones
Biosynthesis Adrenal gland disorders
Brain Glucocorticoids
Cholesterol Cortisol
Corticosteroids Cortisone
Cortisol Pregnenolone
Cortisone
CRH
CYP11A1
CYP11B1
CYP17A1
CYP21A2
Cytokines
Glucocorticoid
Glucocorticoid Receptor
IL 1
Immune System
Immunosuppressive
Inflammatory Disorders
Intestine
LE
Lupus Erythematosus
Membrane
Mitochondria
Multiple Sclerosis
Open Doors
Pregnenolone
Psoriasis
Rheumatoid Arthritis
Side Chain
TNF
Ultraviolet

Semantics

Type Source Name
pathway REACTOME Glucocorticoid biosynthesis
drug DRUGBANK Cholesterol
drug DRUGBANK Pregnenolone
drug DRUGBANK Hydrocortisone
drug DRUGBANK Corticotropin
drug DRUGBANK Cortisone
disease MESH autoimmune diseases
disease MESH multiple sclerosis
disease MESH rheumatoid arthritis
pathway KEGG Rheumatoid arthritis
disease MESH psoriasis
disease MESH atopic dermatitis

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