Tissue-specific ligands

SARMs are AR ligands that display tissue-specific androgenic/antiandrogenic activities. 

Ligand-bound corticosteroid receptors have been shown to interact to form heterodimers with other transcription factors, such as the jun protein. Such interactions are responsible for transactivation of the ds-regulatory sites known as AP-1 sites and for the glucocorticoid-mediated suppression of transcription, such as that seen in the pro-opiomelanocortin gene. A number of such specific protein interactions have been reported these interactions and their locations relative to other transcription factors transform a ubiquitous steroid hormone signal into a tissue-specific, graded cellular response. 

The role of GPR55 is unknown at present. Transcripts have been identified in various human tissues, including brain, spleen, ileum and omental (but not subcutaneous) adipose tissue. This last observation may point to a role in regulation of central adiposity, but blood pressure control has also been suggested as a possible function [88]. Specific ligands and/or knockout animals will be required to probe further the role of this receptor. 

Since the brain expresses many mRNAs that are also found in non-nervous tissue and are therefore of little interest to the psychopharmacologist, it is necessary to isolate only those cDNAs that, for example, encode for a specific enzyme or receptor protein. Several techniques have been developed to achieve this. For example, a specific cDNA plasmid may be inserted into cultured mammalian cells such as fibroblasts that can express the specific receptor or enzyme. Once this has been expressed in the culture medium, the receptor or enzyme can be identified by adding a specific ligand or substrate. This enables those cells that expressed the specific macromolecule of interest to be identified and... 

---