25 Years of Estrogen Receptor Beta: A Personal Journey

September 2021 in “ Journal of molecular endocrinology ”

Margaret Warner, Xiaotang Fan, Anders Ström, Weiqiang Wu, Jan‐Åke Gustafsson

estrogen receptor beta ERβ dihydrotestosterone DHT 5α-androstane-3β, 17β-diol 3βAdiol androgen signaling prostate cancer central nervous system CNS ERβ agonists neurodegenerative diseases Parkinson's multiple sclerosis Alzheimer's splice variants

TLDR ERβ has potential in treating prostate cancer and neurodegenerative diseases, but human studies are needed before clinical use.

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.

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