What are glucocorticoids
The steroids referred to in this study are glucocorticoids. Glucocorticoids (of which cortisol and methylprednisolone are members) are a subclass of a class of biochemical molecules collectively called steroid hormones. All steroid hormones are similar in that they have a backbone structure of cholesterol from which they are all derived. The glucocorticoid cortisol is produced in the adrenal gland upon stimulation of the adrenal cells by another hormone called adrenocorticotropin hormone (ACTH). ACTH is released from the pituitary cells in the brain upon stimulation by the peptide corticotropin releasing factor (CRF) from the hypothalamus also in the brain. The release of CRF and ACTH is under control by a negative feedback of cortisol circulating in the blood.

After a certain level of cortisol, the release of CRF and ACTH are inhibited, therefore down-regulating the amount of cortisol to be synthesized in the adrenal gland. This control is referred to as the hypothalamic pituitary axis (HPA). Cortisol is produced at a higher level in the morning than afternoon, thus a diurnal variation of release of cortisol exists in humans. This variation is a fairly constant range between humans of normal health status. Glucocorticoids are called stress hormone because stress to the body such as various insults of microbial infections, trauma, and excess inflammation upregulates the production of cortisol to a certain level. If this is not sufficient to help fight off the insult through the cellular events, additional glucocorticoids are administered using pharmaceutical doses and forms such as methylprednisolone.

Glucocorticoids are relatively small in size compared to protein hormone molecules and cytokines, which are proteins. The glucocorticoids are secreted directly into circulation immediately after their synthesis. Cortisol, the major human GC, circulates bound (95%) to a corticosteroid-binding globulin (CBG) synthesized primarily in the liver, thereby providing a large reservoir that is released at sites of inflammation or tissue remodelling. The glucocorticoids are released from the CBG at the cell membrane. Glucocorticoids are hydrophobic molecules which are able to cross the plasma membrane of cells by simple diffusion. Once inside the target cell, the glucocorticoid binds tightly but reversibly to a complementary receptor protein (GCR). Glucocorticoids assert most of their effects through specific ubiquitously distributed intracellular GCR (approximately 3,000 to 100,000 per cell), which are found abundantly in diverse genes encoding cytokines as well as other mediators or cellular regulatory elements of the host defense response.
The affinity of a given glucocorticoid for its receptor is a major determinant of its biologic activity. The binding of the hormone causes the receptor protein to undergo conformational changes that increases its affinity for DNA and enables it to bind to a specific gene area called a glucocorticoid response element (GRE) in the nucleus and regulates the transcription of that gene to mRNA. The mRNA is then translated to protein in the cell’s expression system.

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