Glucocorticoids & Receptors

Glucocorticoids

Glucocorticoids are a class of steroid hormones present in almost every vertebrate animal cell. They have several roles:

metabolism of glucose
anti-inflammatory response
promoting maturation of the lungs in fetal development
arousal and cognition
used to treat diseases such as allergies, asthma, and autoimmune diseases

Glucocorticoid receptors are in the cytoplasm and have heat shock proteins attached to them. Once the hormone is inside the cell, it binds to the glucocorticoid receptors at the ligand binding domain and causes a conformational change where the heat shock proteins come off. The hormone and the GR form a GR complex. This complex travels into the nucleus and activates transcription and translation by binding to the DNA at the DNA binding domain. The complex can express inflammatory proteins in the nucleus by means of trans-activation, or it can repress inflammaotry proteins by means of trans-repression. Glucocorticoids have specific target cells and receptors that they bind to, which causes specific effects on the cell.

Cortisol is the most common glucocorticoid and is essential for life. It supports and regulates cardiovascular, metabolic, immunologic, and homeostatic functions. If there is blockage of the GR, and cortisol cannot bind to them, this can prevent the recall of emotionally relevant information. On the other hand, if there are high levels of cortisol, it can increase stress and inhibit the retrieval of stored information.

Glucocorticoid Receptors

Glucocorticoid receptors are nuclear receptors found in the body. Nuclear receptors are a class of proteins found in cells that sense steroids and hormones and cause the cell to respond appropriately. GR are a part of subfamily 3, group C, member 1 (NR3C1 gene). Cortisol and other glucocorticoids bind to these receptors. They are expressed in almost every cell. In humans, the NR3C1 gene is on chromosome 5 (5q31). There are several domains of the GR:

A/B domain- N terminal; highly variable among nuclear receptors
C domain- DNA binding domain (DBD); highly conserved domain; contains two zinc fingers that bind to specific sequences of DNA called hormone response elements
D domain- hinge region; flexible domain that connects DNA binding domain with the ligand binding domain
E domain- ligand binding domain (LBD); moderately conserved in sequence and highly conserved in structure; where the hormones or steroids bind
F domain- C terminal domain; variable in sequence