Prostate Development: Mechanisms for Opposite Effects of Low and High Doses of Estrogenic Chemicals
Rajesh K. Naz in Endocrine Disruptors, 2004
Estradiol can directly bind and activate androgen receptor (AR) in the presence of the co-activator ARA70.90 In the LNCaP prostate cancer cell line, either estrogen or androgen can activate formation of a complex of AR, estrogen receptor (ER), and Src, and thus induce cell proliferation through the Src-Ras-Erks pathway.96 AR activates PAK6 kinase activity, and PAK6 inhibits transcriptional activation by AR and ER.97 Estrogen receptor alpha (ERα) can directly bind AR and alter transcriptional activation by AR.88,98 Finally, estrogen alters AR expression levels in a tissue-specific manner.99–101 Analysis of gene expression patterns in adult human prostate stroma cells in response to a high dose of estradiol revealed hundreds of estrogen-regulated genes.95 Estrogen treatment thus has pleiotropic effects, both in vivo and in vitro. Many “housekeeping” genes are up-regulated by estradiol, including the ribosomal protein RBP and the cytoskeleton protein vimentin.92
Formulated Natural Selective Estrogen Receptor Modulators: A Key To Restoring Women’s Health
Megh R. Goyal, Durgesh Nandini Chauhan in Plant- and Marine-Based Phytochemicals for Human Health, 2018
Estrogen (American English) or oestrogen (British English) is a significant sex hormone to regulate the growth, development, and physiology of the human reproductive system.18, 74 Estrogens also affect the activity of neuroendocrine, skeletal, adipogenesis, and cardiovascular systems.96 The biological functions of estrogen are mediated by binding to the ERs: estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). Estrogen signaling is selectively stimulated or inhibited depending upon a balance between ERα and ERβ activities in target organs. Further, these receptors are transcriptional factors to regulate the expression of specific genes in different tissues in aligned-dependent manner. Estrogens are small, carbon-rich molecules built from cholesterol.
Chemopreventive Agents
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
Increased levels of circulating estrogen have been shown to enhance the risk of developing breast and endometrial cancers, with approximately 70% of breast cancers categorized as estrogen-receptor (ER) positive and that can be treated with antiestrogen therapies. Estrogen has been shown to play a vital role in the early-stage development and proliferation of epithelial cells that precedes ER-positive invasive breast cancer. Estrogen can increase the risk of breast and endometrial cancers via several different molecular mechanisms, including a reduced level of apoptosis. The situation is further complicated by the fact that, although Estrogen Receptor Alpha (ER-α) is elevated in several cancer cell types and acts to induce cellular proliferation, Estrogen Receptor Beta (ER-β) has demonstrated protective effects by inhibiting proliferation.
High serum concentration of estradiol may be a risk factor of prostate enlargement in aging male in China
Published in The Aging Male, 2020
Ding Xu, Yu Wu, Haibo Shen, Subo Qian, Jun Qi
In the estrogen pathway, estrogen receptors play an important role in modulating estrogen action. Estrogen action is mediated by two nuclear receptors: estrogen receptor-alpha (ERα) and estrogen receptor-beta (ERβ). ERα is a key mediator and putative therapeutic target for bladder complications of BPH. It has been reported that, while ERα is an oncogenic factor involved in cell proliferation and survival, ERβ is a protective factor that is anti-carcinogenic and pro-apoptotic. Recent experimental animal models on prostatic hyperplasia support estrogen receptors as critical factors in the prostatic hyperplastic response [29]. E2 has been shown to promote prostate proliferation through activating ERα [9] and cells expressing ERα were more prevalent in human BPH [30]. Moreover, Park et al. suggested that the mechanism of estrogen-regulated cell growth and the role of stromal cells may be different in normal versus BPH prostates. Normal stromal cells predominantly used rapid E2 signaling, but BPH stromal cells used classical ER-signaling, which was inhibited by treatment with ER antagonist [31]. To some extent, these may explain why the higher serum E2 level, the higher prostate volume in BPH patients.
Prediagnostic use of estrogen-only therapy is associated with improved colorectal cancer survival in menopausal women: a Swedish population-based cohort study
Published in Acta Oncologica, 2021
Johanna Simin, Qing Liu, Xinchen Wang, Katja Fall, Cecilia Williams, Steven Callens, Lars Engstrand, Nele Brusselaers
In addition to lower incidence among women, CRC-mortality is one-fourth lower among women than men, indicating for a potential role of sex hormones (and particularly estrogens) in CRC progression [1,3,4]. Two nuclear receptors, estrogen receptor alpha (ERα) and beta (ERβ) mediate effects of estrogen. ERβ in normal colon epithelia has been experimentally shown to play a role in the prevention of a tumor formation in mouse models, by reducing inflammation of the gut [5]. Furthermore, in-vivo mice-models suggest exogenous estrogens impacting inflammatory markers and reducing proliferation of the crypt [5,6], and changing gut microbiota diversity in CRC-induced males [7]. As this posed link of estrogens with gut inflammation and microbiome might be modifiable, it could contribute to a reduced CRC risk [7], and potentially improved survival.
COL1A1, CCDC170, and ESR1 single nucleotide polymorphisms associated with distal radius fracture in postmenopausal Mexican women
Published in Climacteric, 2020
E. Farias-Cisneros, A. Hidalgo-Bravo, A. Miranda-Duarte, L. Casas-Ávila, T. D. Rozental, R. Velázquez-Cruz, M. Valdés-Flores
Type 1 collagen is the most abundant protein in mammals and is the main structural component of bone, teeth, and tendon21. The molecular structure of the protein comprises two alpha chains, encoded by the COL1A1 gene, and one beta chain, encoded by the COL1A2 gene8. The product of the estrogen receptor alpha gene (ESR1) is a ligand-activated transcription factor. Estrogens and estrogen receptors have an important role in bone homeostasis22. A population-based study found the rs4870044 SNP located at the CCDC170/C6ORF97/ESR1 locus (6q25.1) to be associated with forearm and total hip BMD23. The function of the product of the coiled-coil domain containing 170 gene (CCDC170) is not yet fully understood. Experimental evidence suggests that it participates in organization of the Golgi apparatus24,25. Several genome-wide association studies have implicated the region around this gene to be involved in breast cancer and BMD, including one study in Mexican mestizo women26,27.
Related Knowledge Centers
- Activator
- Estrogen
- Estrogen Receptor
- Ligand
- Nuclear Receptor
- Protein Domain
- Gene
- Transcription Factor
- DNA-Binding Domain
- Transcription