Molecular mechanisms of estrogen action: selective ligands and receptor pharmacology

Katzenellenbogen, Benita S.; Choi, Inho; Delage-Mourroux, Régis; Ediger, Tracy R.; Martini, Paolo; Montano, Monica M.; Sun, Jun; Weis, Karen E.; Katzenellenbogen, John A.

doi:10.1016/s0960-0760(00)00104-7

Cited by 264 publications

(186 citation statements)

References 52 publications

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“…Simpkins and colleagues have led the field in developing nonfeminizing estrogens (Simpkins et al, 2005), and the chemical synthesis efforts of Katzenellebogen and colleagues has been instrumental in developing ER␣-and ER␤-selective ligands (Katzenellenbogen et al, 2000;Meyers et al, 2001). In the industrial sector, Wyeth (Princeton, NJ), Eli Lilly & Company (Indianapolis, IN), Pfizer (New York, NY), and others all have ET or HT development efforts that are now conscious of the importance of the neural effects of these therapeutics (Zhao et al, 2005a;Ariazi et al, 2006).…”

Section: Translating Basic Neuroscience Insights Into Safe and Efficamentioning

confidence: 99%

Estrogen, Menopause, and the Aging Brain: How Basic Neuroscience Can Inform Hormone Therapy in Women

Morrison¹,

Brinton²,

Schmidt³

et al. 2006

J. Neurosci.

312

242

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IntroductionAs neuroscientists, we can be so taken by the complexity and unique capabilities of the brain that we occasionally forget that it is part of a larger integrated biological system reliant on signaling and communication throughout the organism. The interactions between key organs that release hormones (e.g., gonads) and the nervous system are an excellent reflection of this "whole-brain, whole-body" level of integration. For example, effects of estrogens such as 17-␤-estradiol (the major estrogen in most mammals, including women, referred to henceforward as estradiol) on a broad array of brain regions and the widespread distribution of estrogen receptors throughout the entire brain highlight the extraordinary integrative power of this hormone. An important concept in this interaction is that the brain both controls estrogen release through the hypothalamus-pituitary-gonadal (HPG) axis and responds to estrogen. Neuroendocrine function initiates in the hypothalamus (see below, section by A.C.G.) (Fig. 1), but the circuits that respond to estrogens go well beyond the hypothalamus to include neocortex, hippocampus, and brainstem. In addition, estradiol plays a key role in the neurobiology of aging, because endocrine and neural senescence overlap in time and are mechanistically intertwined in complex feedback loops. This aspect of aging is fundamental for humans, because all women will experience a dramatic drop in circulating estrogens if they live long enough to reach the menopause transition. Interestingly, at the turn of the past century, both life expectancy and the average age of onset of menopause for women in America was slightly over 50 years, whereas currently women can expect to live until 80 years of age, although the average age of menopause remains in

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Section: Translating Basic Neuroscience Insights Into Safe and Efficamentioning

confidence: 99%

Estrogen, Menopause, and the Aging Brain: How Basic Neuroscience Can Inform Hormone Therapy in Women

Morrison¹,

Brinton²,

Schmidt³

et al. 2006

J. Neurosci.

312

242

View full text Add to dashboard Cite

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“…We hypothesized that a promoter with allele C, which cannot be recognized as a TATA sequence and also as binding side for GATA or STAF becomes more accessible for EREF and VDR/RXR (Table 4), which may induce LTF gene expression. The EREF Tf functions under the influence of the reproductive hormone estrogen (Katzenellenbogen et al 2000, Teng 2002. VDR/RXR is a multi-domain protein and nuclear receptor (NR) of vitamin D and functions as an obligate heterodimer with the retinoid X receptor (RXR) (Zhang et al 2011, Gocek et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Association of polymorphism within LTF gene promoter with lactoferrin concentration in milk of Holstein cows

Zabolewicz¹,

Barcewicz²,

Brym³

et al. 2014

Polish Journal of Veterinary Sciences

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This study analyzed the association between single nucleotide polymorphism (A/C) in position -28 located in the TATA box of LTF gene and the lactoferrin concentration in bovine milk secreted by healthy and infected udders. Out of 241, 69 cows were selected into the experimental group and were divided into 3 groups according to mean value of somatic cell count (SCC): I <180 000 cells/mL, II: 180 000 -350 000 cells/mL and III > 350 000 cells/mL. In each SCC group, three LTF genotypes: AA, AC and CC were identified by PCR-SSCP method. A total of 604 milk samples were collected monthly and lactoferrin concentration was measured by ELISA. The 1-way ANOVA within SCC groups was performed to estimate association of -28 A/C genotypes with mean lactoferrin concentration per lactation. In the group of healthy cows (<180 000 cells/mL) LTF concentration in milk cows with the AA genotype (107.58 ± 17.92 μg/mL) was significantly higher than in homozygotes CC (52.09 ± 19.01 μg/mL). Unexpectedly, in cows with elevated SCC (>350 000 cells/mL) we observed a significant opposite relationship (207.21 ± 28.50 in CC vs 115.0 ± 28.6 μg/mL in AA). We hypothesized that a promoter with allele C, which cannot be recognized as a TATA sequence is becoming more accessible for other transcription factors, which may induce alternative LTF gene expression. We assume that our results demonstrate a very interesting effect of differential gene expression depending on polymorphism in a key regulatory motif (TATA box) and also on the health status of mammary tissues.

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“…This implies a plasticity of ER function that is independent of ER expression levels or mutations and may involve changes in the ER coregulatory machinery. Furthermore, it has been proposed that the selectivity and tissue-specific actions of selective estrogen receptor modulators may be due to variations in coregulator composition (51,52). Evidence for the importance of coregulator levels in ER function include the finding that the coactivator SRC-3 is amplified in breast cancer (53) and that disparate expression of SRC-1 in uterine and breast cancer cells may in part explain the tissue-specific effects of selective estrogen receptor modulators (52).…”

Section: Discussionmentioning

confidence: 99%

Limiting Effects of RIP140 in Estrogen Signaling

White¹,

Yore

Deng

et al. 2005

Journal of Biological Chemistry

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The receptor interacting protein 140 (RIP140) belongs to a unique subclass of nuclear receptor coregulators with the ability to bind and repress the action of a number of agonist-bound hormone receptors. We have previously demonstrated that all-trans-retinoic acid (RA) induction of RIP140 constitutes a rate-limiting step in the regulation of retinoid receptor signaling. Here we demonstrate that RIP140 is also a limiting regulator of estrogen receptor signaling. Overexpression of RIP140 dose dependently inhibits estrogen-dependent reporter activity in human breast cancer cells. Furthermore, small interfering RNA to RIP140 enhances estrogen-dependent signaling. Our previous studies indicate that RIP140 is a direct target of RA. We report here that RA can abrogate estrogen-mediated cell cycle re-entry. In addition, RA treatment of estrogen-dependent breast cancer cells opposes estrogen receptor-dependent reporter activity, implying that a proportion of RA effects are anti-estrogenic. We provide evidence for a role for RIP140 in mediating anti-estrogenic effects of RA. RIP140 small interfering RNA blocks RA-mediated repression of estrogen receptor activity and provides a growth advantage to estrogen-dependent cells. Together these data implicate a regulatory role for RIP140 in mediating anti-estrogenic effects of RA in estrogendependent breast cancer cells and suggest that acute regulation of coregulator expression may be a general mechanism to integrate diverse hormone signals.

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Molecular mechanisms of estrogen action: selective ligands and receptor pharmacology

Cited by 264 publications

References 52 publications

Estrogen, Menopause, and the Aging Brain: How Basic Neuroscience Can Inform Hormone Therapy in Women

Estrogen, Menopause, and the Aging Brain: How Basic Neuroscience Can Inform Hormone Therapy in Women

Association of polymorphism within LTF gene promoter with lactoferrin concentration in milk of Holstein cows

Limiting Effects of RIP140 in Estrogen Signaling

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