Tissue-Specific Effects of Loss of Estrogen during Menopause and Aging

Wend, Korinna; Wend, Peter; Krum, Susan A.

doi:10.3389/fendo.2012.00019

Cited by 98 publications

(72 citation statements)

References 216 publications

(227 reference statements)

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“…Both the receptors have a ligand-binding domain that can bind estrogen or an SERM. [21][22][23][24] After binding, the receptors dimerize and recruit other factors involved in controlling the expression of estrogen-regulated genes. [21][22][23][24] A critical factor controlling the agonistic or antagonistic tissue effects of ERs is the availability of coinducers and corepressors in each tissue type as well as their binding to the ERs.…”

Section: Introductionmentioning

confidence: 99%

“…[21][22][23][24] After binding, the receptors dimerize and recruit other factors involved in controlling the expression of estrogen-regulated genes. [21][22][23][24] A critical factor controlling the agonistic or antagonistic tissue effects of ERs is the availability of coinducers and corepressors in each tissue type as well as their binding to the ERs. 22,23,25 Each SERM induces unique conformational changes in ERs, which can affect the relative binding of coactivators and corepressors.…”

Section: Introductionmentioning

confidence: 99%

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Profile of Ospemifene in the Breast

Berga

2013

Reprod. Sci.

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Vulvar and vaginal atrophy (VVA) is a chronic, progressive medical condition prevalent among postmenopausal women, which produces symptoms such as dyspareunia, vaginal dryness, and vaginal irritation. Currently, the only prescription options are systemic and vaginal estrogen therapies that may be limited by concerns about long-term safety and breast cancer risk. Ospemifene is a tissue-selective estrogen agonist/antagonist (a selective estrogen receptor modulator) recently approved by the US Food and Drug Administration for treatment of dyspareunia, a symptom of VVA, due to menopause. Ospemifene, the first nonestrogen oral treatment for this indication, may provide an alternative to treatment with estrogen. Animal models with ospemifene suggest an inhibitory effect on growth of malignant breast tissue, but animal data cannot necessarily be extrapolated to humans. Clinical trials, including 3 long-term studies assessing the overall safety of ospemifene, support that ospemifene is generally well tolerated, with beneficial effects on the vagina, neutral effects on the breast, and minimal effects on the endometrium.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Profile of Ospemifene in the Breast

Berga

2013

Reprod. Sci.

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“…PBMCs are not, despite literature suggests that they display ERs Wend et al, 2012). Again, for ER genes the effect size in rats (26.7%) was ~5 times greater than in humans (5%).…”

Section: Discussionmentioning

confidence: 87%

A risk assessment-driven quantitative comparison of gene expression profiles in PBMCs and white adipose tissue of humans and rats after isoflavone supplementation

Velpen

Veer

Islam

et al. 2016

Food and Chemical Toxicology

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Quantitative insight into species differences in risk assessment is expected to reduce uncertainty and variability related to extrapolation from animals to humans. This paper explores quantification and comparison of gene expression data between tissues and species from intervention studies with isoflavones.Gene expression data from peripheral blood mononuclear cells (PBMCs) and white adipose tissue (WAT) after 8wk isoflavone interventions in postmenopausal women and ovariectomized F344 rats were used. A multivariate model was applied to quantify gene expression effects, which showed 3 to 5-fold larger effect sizes in rats compared to humans.For estrogen responsive genes, a 5-fold greater effect size was found in rats than in humans.For these genes, intertissue correlations (r=0.23 in humans, r=0.22 in rats) and interspecies correlation in WAT (r=0.31) were statistically significant. Effect sizes, intertissue and interspecies correlations for some groups of genes within energy metabolism, inflammation and cell cycle processes were significant, but weak.Quantification of gene expression data reveals differences between rats and women in effect magnitude after isoflavone supplementation. For risk assessment, quantification of gene expression data and subsequent calculation of intertissue and interspecies correlations within biological pathways will further strengthen knowledge on comparability between tissues and species.

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“…The presence of both types of oestrogen receptors was observed in the fallopian tubes, vagina, thyroid gland, bones, and brain [14,15].…”

Section: Prace Poglądowementioning

confidence: 97%

“…Obecność obu typów receptorów estrogenowych stwierdzono w jajowodach, pochwie, gruczole tarczowym, kościach i mózgu [14,15].…”

Section: Polish Versionunclassified

The polymorphism of estrogen receptor α is important for metabolic consequences associated with menopause

Pinkas

Gujski

Wierzbińska-Stępniak

et al. 2016

Endokrynologia Polska

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The menopause is associated with multiple health and metabolic consequences resulting from the decrease in oestrogen levels. Women at postmenopausal age are burdened with a higher risk of cardiovascular diseases, and the main cause of mortality in this group is ischaemic heart disease. Oestrogen deficiency is related, among other things, with frequent occurrence of dyslipidaemia, cessation of the beneficial effect of oestrogens on the vascular wall, and increase in body weight characterised by unfavourable redistribution of fatty tissue, with an increased amount of visceral fat and reduction of so-called non-fatty body mass. Oestrogens exert an effect on the metabolism, mainly through the genomic mechanism. The presence of a and b oestrogen receptors was found in many tissues and organs. Recently, attention has been paid to the fact that the effect of oestrogen action on tissues and organs may depend not only on their distribution, but also on their polymorphic types. This article presents the latest approach to the problem of metabolic consequences resulting from menopause, according to the possessed a oestrogen receptor polymorphism (ERa). Genes encoding for ERa have many polymorphic variants, the most important of which from the clinical aspect are two single nucleotide polymorphisms (SNPs): Xba1 and PvuII. The review of literature indicates that ERa polymorphisms are of great importance with respect to the effect of oestrogens on the functioning of the body of a woman after menopause, and may imply the development of many pathological states, including the prevention or development of metabolic disorders. Identifying ERa polymorphisms may be useful in oestrogen therapy for menopausal women who may benefit from it. (Endokrynol Pol 2016; 67 (6): 608-614) Key words: menopause; oestrogen receptor; metabolic disorders StreszczenieMenopauza związana jest z wieloma zdrowotnymi i metabolicznymi konsekwencjami wynikającymi ze spadku poziomu estrogenów. Kobiety w wieku pomenopauzalnym są obarczone wyższym ryzykiem chorób sercowo-naczyniowych, a główną przyczyną śmiertelności w tej grupie jest choroba niedokrwienna serca. Niedobór estrogenów związany jest między innymi z częstym występowaniem dyslipidemii, przerwaniem korzystnego oddziaływania estrogenów na ściany naczyń, zwiększeniem masy ciała charakteryzującym się niekorzystnym rozmieszczeniem tkanki tłuszczowej o zwiększonej ilości tłuszczu trzewnego i redukcji tak zwanej beztłuszczowej masy ciała. Estrogeny wywierają wpływ na metabolizm głównie poprzez mechanizm genomowy. Obecność receptorów estrogenowych a i b została stwierdzona w wielu tkankach i narządach. Ostatnio zwrócono uwagę na fakt, że efekt działania estrogenów na tkanki i narządy może zależeć nie tylko od rozkładu, ale również od rodzaju ich typów polimorficznych. W artykule przedstawiono najnowsze podejście do problemu metabolicznych następstw wynikających z menopauzy, w zależności od posiadanego polimorfizmu receptora estrogenowego alfa (ERa). Geny kodujące ERa mają wiele wariantów polimorfic...

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Tissue-Specific Effects of Loss of Estrogen during Menopause and Aging

Cited by 98 publications

References 216 publications

Profile of Ospemifene in the Breast

Profile of Ospemifene in the Breast

A risk assessment-driven quantitative comparison of gene expression profiles in PBMCs and white adipose tissue of humans and rats after isoflavone supplementation

The polymorphism of estrogen receptor α is important for metabolic consequences associated with menopause

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