Glucocorticoid-inducible system

Glucocorticoids induce cataract formation, particularly in patients with rheumatoid arthritis. An increase in intraocular pressure related to a decreased outflow of aqueous humor is also a frequent side effect of periocular, topical, or systemic administration. Induction of ocular hypertension, which occurs in about 35% of the general population after glucocorticoid administration, depends on the specific drug, the dose, the frequency of administration, and the glucocorticoid responsiveness of the patient. 

M.C. Bohn, Glucocorticoid induced teratologies of the nervous system, in in J. Yanai (Ed.), Neurobehavioral Teratology, Elsevier, Amsterdam, 1984, pp. 365-387. 

Topical and systemic treatment with glucocorticoids induces atrophy of skin, bone, as well as a number of other organs, with a concomitant decrease in GAGs, in particular HA. In human skin organ cultures, hydrocortisone has a bimodal effect. At low physiological concentrations, 10-9 M,... 

T-cell activity, thereby terminating the inflammation of the central nervous system [75]. Moreover, corticoids may reduce allergen specific T-cells through apoptosis, which is one of the mechanisms of effectiveness of corticoids in asthmatics [76], as well as induce apoptosis of endomysial T-cells in human idiopathic polymyositis, thus modifying the inflammation [77]. Interestingly, the expression of Bcl-2 may be an important factor in protecting the lymphocytes in inflamed synovial membranes from glucocorticoid-induced apoptosis [78]. 

PNMT catalyzes the N-methylation of norepinephrine to form epinephrine in the epinephrine-forming cells of the adrenal medulla. Since PNMT is soluble, it is assumed that norepinephrine-to-epinephrine conversion occurs in the cytoplasm. The synthesis of PNMT is induced by glucocorticoid hormones that reach the medulla via the intra-adrenal portal system. This special system provides for a 100-fold steroid concentration gradient over systemic arterial blood, and this high intra-adrenal concentration appears to be necessary for the induction of PNMT. 

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