25 Years of Estrogen Receptor Beta: A Personal Journey

The document discusses the discovery of estrogen receptor beta (ERβ) and its implications in estrogen signaling, particularly highlighting the role of dihydrotestosterone (DHT) as a precursor to an ERβ agonist, 5α-androstane-3β, 17β-diol (3βAdiol). ERβ has been shown to counteract androgen signaling, suggesting its potential as a treatment target for prostate cancer. Additionally, ERβ has effects in the central nervous system (CNS) that are independent of androgen signaling. While ERβ agonists have been effective in rodent models of neurodegenerative diseases, such as Parkinson's, multiple sclerosis, and Alzheimer's, these results have not been replicated in humans. The review emphasizes the need for further research on ERβ signaling in humans or primates before considering the clinical use of ERβ agonists, due to significant differences in ERβ signaling and splice variants between humans and rodents.