Key Event Relationship Description
Provide a brief, descriptive summation of the KER. While the title itself is fairly descriptive, this section can provide details that aren’t inherent in the description of the KEs themselves (see page 39 of the User Handbook). This description section can be viewed as providing the increased specificity in the nature of upstream perturbation (KEupstream) that leads to a particular downstream perturbation (KEdownstream), while allowing the KE descriptions to remain generalised so they can be linked to different AOPs. The description is also intended to provide a concise overview for readers who may want a brief summation, without needing to read through the detailed support for the relationship (covered below). Careful attention should be taken to avoid reference to other KEs that are not part of this KER, other KERs or other AOPs. This will ensure that the KER is modular and can be used by other AOPs.
Dihydrotestosterone (DHT) is, together with testosterone, a primary ligand for the Androgen receptor (AR). DHT is an endogenous sex hormone that is synthesis from e.g. testosterone by the enzyme 5α-reductase in selected tissues, not least in the reproductive tracts of both sexes, but also other tissues and organs (Davey & Grossmann, 2016; Marks, 2004). In the absence of ligand (DHT/testosterone) the AR is localized in the cytoplasm. AR is only activated and translocated into the nucleus to carry out its ‘genomic function’ upon ligand binding (Davey & Grossmann, 2016). Hence, AR transcriptional function is directly dependent on the presence of ligands, with DHT being a more potent AR activator (2-fold higher binding affinity) than testosterone (Grino et al, 1990). Reduced levels of DHT will lead to reduced AR activation.