Steroid receptor coactivator-1: The central intermediator linking multiple signals and functions in the brain and spinal cord

The effects of steroid hormones are believed to be mediated by their nuclear re-ceptors (NRs). The p160 coactivator family, including steroid receptor coactivator-1 (SRC-1), 2 and 3, has been shown to physically interact with NRs to enhance their transactivational ac-tivities. Among which SRC-1 has been predominantly localized in the central nervous system including brain and spinal cord. It is not only localized in neurons but also detectable in neuro-glial cells (mainly localized in the nuclei but also detectable in the extra-nuclear components). Although the expression of SRC-1 is regulated by many steroids, it is also regulated by some non-steroidal factors such as injury, sound and light. Functionally, SRC-1 has been implied in normal function such as development and ageing, learning and memory, central regulation on reproductive behaviors, motor and food intake. Pathologically, SRC-1 may play a role in the regulation of neuropsychiatric disorders (including stress, depression, anxiety, and autism spectrum disorder), metabolite homeostasis and obesity as well as tumorigenesis. Under most conditions, the related mechanisms are far from elucidation; although it may regulate spatial memory through Rictor/mTORC2-actin polymerization related synaptic plasticity. Several in-hibitors and stimulator of SRC-1 have shown anti-cancer potentials, but whether these small molecules could be used to modulate ageing and central disorder related neuropathology remain unclear. Therefore, to elucidate when and how SRC-1 is turned on and off under different stimuli is very interesting and great challenge for neuroscientists.Copyright 2021, Chongqing Medical University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/ 4.0/).

Automated summary

The effects of steroid hormones are mediated by their nuclear receptors. The p160 coactivator family interacts with nuclear receptors to enhance their transcriptional activities. SRC-1, predominantly localized in the central nervous system, is regulated by steroids and non-steroidal factors. It plays important roles in normal function and pathophysiology, but its mechanisms are not fully understood.