Glucocorticoids

Glucocorticoids are corticoid substances (cortisol, cortisone, and corticosterone) that increase the concentration of liver glycogen and blood sugar. They belong to five major classes of steroid hormones which also include progestagens, mineralocorticoids, androgens, and estrogens. These substances, also known as corticosteroids, glucocorticoid agonists, steroids, and asthma controllers, are widely used as anti-inflammatory agents.

Importance of Glucocorticoids

Mice with a disrupted GR gene lack a functional receptor and die shortly after birth, indicating that a functional glucocorticoid signaling pathway is essential for life. Corticosteroids affect all of the major systems of the body, including the cardiovascular, musculoskeletal, nervous, and immune systems, and play critical roles in fetal development including the maturation of the fetal lung. Because so many systems are sensitive to corticosteroid levels, tight regulatory control is exerted on the system. The direct effects of corticosteroids are sometimes difficult to separate from their complex relationship with other hormones, in part due to the permissive action of low levels of corticosteroid on the effectiveness of other hormones, including catecholamines and glucagon. Nevertheless, the effects of corticosteroids can be classified into two general categories: glucocorticoid (intermediary metabolism, inflammation, immunity, wound healing, myocardial, and muscle integrity) and mineralocorticoid (salt, water, and mineral metabolism).

Natural glucocorticoids (cortisol) are released from the adrenal gland in response to stress. When in excess glucocorticoids can cause catabolism of muscle and release of amino acids; these are subsequently used to increase glucose synthesis by the liver (gluconeogenesis). They also enhance the degradation of fat. The most important function of glucocorticoids in disease is to regulate the inflammatory response to external factors. Glucocorticoid drugs have been used for many decades in the treatment of many inflammatory and immune diseases and disorders. 2

Glucocorticoids exert their effects by binding to cytoplasmic receptors (GR) which are present in almost all cell types. GRs produce their effects on responsive cells by stimulating GRs by directly or indirectly regulate the transcription of target genes. Glucocorticoids may suppress inflammation by increasing the synthesis of anti-inflammatory proteins.

Inspite of the ability of glucocorticoids to induce gene transcription, the major anti-inflammatory effects of glucocorticoids are through repression of inflammatory and immune genes.

Clinical Use of Glucocorticoids

Glucocorticoids are widely used to treat a variety of inflammatory and immune diseases, including asthma. Available glucocorticoid drugs include betamethasone, cortisone, dexamethasone, fluprednisolone, hydrocortisone, meprednisone, methylprednisolone, paramethasone, prednisolone, prednisone, and triamcinolone.

Glucocorticoids are frequently used in the treatment of nonhematologic malignancy to relieve symptoms of cancer and its treatment. For example, glucocorticoids prevent vomiting and allergic reactions associated with cancer therapy. Glucocorticoids decrease edema in CNS malignancy, and can decrease pain secondary to cancer.

Glucocorticoids are part of the treatment of some cancers. Glucocorticoids, as monotherapy and in combination with ketoconazole or chemotherapy, are used in prostate cancer. They are an option for postmenopausal women with breast cancer. Thymomas are another indication for glucocorticoids. Lymphoma and multiple myeloma can respond to glucocorticoids.