This pathway delineates genes involved in steroid biology at three different levels:
- the hypothalamic-anterior pituitary-adrenal axis which sets the level of circulating glucocorticoid in the body,
- the effects of glucocorticoid on peripheral tissues including the CNS, heart, lung, gut and other organs at the surface of these cells and
- the activation of transcriptionally regulated nuclear elements in these tissues where cellular processes such as inflammation are controlled.
In the HPA view, we have focused on the actions of corticotropin releasing factor (CRH) and Urocortin (UCN) on the anterior pituitary and peripheral tissues, in particular the adrenal gland where endogenous glucocorticoids are released. Stresscopin (UCN3) and stresscopin related peptide (UCN2) are also made in hypothalamic and extrahypothalamic areas, and the receptors CRHR1 and CRHR2 are also present in the hypothalamus, however these circuits and their relationships are still unclear.
The Pharmacodynamics view depicts the actions of endogenous glucocorticoids and glucocorticoid drugs, such as prednisone, on the peripheral tissues. This is of particular relevance to treatment of inflammatory diseases such as asthma, inflammatory bowel disease and arthritis. Clicking on the gene regulatory complex focuses in on the regulation of transcription by glucocorticoids and their receptors, and then clicking on "glucocorticoid responsive genes" bring up a list of references for these relationships which can be downloaded in excel format.
M. Whirl-Carrillo, E.M. McDonagh, J. M. Hebert, L. Gong, K. Sangkuhl, C.F. Thorn, R.B. Altman and T.E. Klein. "Pharmacogenomics Knowledge for Personalized Medicine" Clinical Pharmacology & Therapeutics (2012) 92(4): 414-417. Full text
If you would like to reproduce this PharmGKB pathway diagram: