Estrogen receptor (ER) activity regulates diverse physiological processes via transcriptional modulation of target genes [1]. The selection of target genes and the magnitude of the response, be it induction or repression, are determined by many factors, including the effect of the hormone ligand and DNA binding on ER structural conformation, and the local cellular regulatory environment. The cellular environment defines the specific complement of DNA enhancer and promoter elements present and the availability of coregulators to form functional transcription complexes. Together, these determinants control the resulting biological response.

R,R-THC exhibits partial agonist activity at ERα [8,14]. Estrogen receptors may be blocked non-selectively by tamoxifen and raloxifene and labelled by [³H]17β-estradiol and [³H]tamoxifen. Many agents thought initially to be antagonists at estrogen receptors appear to have tissue-specific efficacy (e.g. Tamoxifen is an antagonist at estrogen receptors in the breast, but is an agonist at estrogen receptors in the uterus), hence the descriptor SERM (selective estrogen receptor modulator) or SnuRM (selective nuclear receptor modulator). Y134 has been suggested to be an ERα-selective estrogen receptor modulator [11].

* Key recommended reading is highlighted with an asterisk

* Coons LA, Hewitt SC, Burkholder AB, McDonnell DP, Korach KS. (2017) DNA Sequence Constraints Define Functionally Active Steroid Nuclear Receptor Binding Sites in Chromatin. Endocrinology, 158 (10): 3212-3234. [PMID:28977594]

* Dahlman-Wright K, Cavailles V, Fuqua SA, Jordan VC, Katzenellenbogen JA, Korach KS, Maggi A, Muramatsu M, Parker MG, Gustafsson JA. (2006) International Union of Pharmacology. LXIV. Estrogen receptors. Pharmacol Rev, 58 (4): 773-81. [PMID:17132854]

* Gonzalez-Sanchez E, Firrincieli D, Housset C, Chignard N. (2015) Nuclear receptors in acute and chronic cholestasis. Dig Dis, 33 (3): 357-66. [PMID:26045270]

* Hewitt SC, Winuthayanon W, Korach KS. (2016) What's new in estrogen receptor action in the female reproductive tract. J Mol Endocrinol, 56 (2): R55-71. [PMID:26826253]

* Jameera Begam A, Jubie S, Nanjan MJ. (2017) Estrogen receptor agonists/antagonists in breast cancer therapy: A critical review. Bioorg Chem, 71: 257-274. [PMID:28274582]

* Warner M, Huang B, Gustafsson JA. (2017) Estrogen Receptor β as a Pharmaceutical Target. Trends Pharmacol Sci, 38 (1): 92-99. [PMID:27979317]

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Subcommittee members: Kenneth S. Korach, Ph.D. Laboratory of Reproductive and Developmental Toxicology NIEHS/NIH 111 TW Alexander Dr. Research Triangle Park, NC 27709 USA Laurel Coons Department of Pharmacology and Cancer Biology Duke University Medical Center Durham, North Carolina 27710 USA