Increases in mouse uterine heat shock protein levels are a sensitive and specific response to uterotrophic agents.

Papaconstantinou, Andriana D.; Fisher, Benjamin R.; Umbreit, Thomas H.; Brown, Ken M.

doi:10.1289/ehp.021101207

Cited by 16 publications

(6 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Uterine weight increases in response to estrogen or estrogen-mimicking compounds [41-42], and this may occur through cross-talk between estrogen and PPARs [23]. An increase in uterine weight could be explained by an increase in PPAR activation related to an increase in estrogen synthesis by preantral and antral follicles present in the ovaries of mice at these two time-points.…”

Section: Discussionmentioning

confidence: 99%

Prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP) affects reproductive outcomes in female mice

Niermann

Rattan

Brehm

et al. 2015

Reproductive Toxicology

View full text Add to dashboard Cite

This study tested the hypothesis that prenatal DEHP exposure affects female reproduction. To test this hypothesis, pregnant female CD-1 mice were orally dosed daily with tocopherol-stripped corn oil (vehicle control) or DEHP (20μg/kg/day-750mg/kg/day) from gestation day 11-birth. Pups were counted, weighed, and sexed at birth, ovaries were subjected to evaluations of follicle numbers on postnatal days (PNDs) 8 and 21, and fertility was evaluated at 3-9 months. The results indicate that prenatal DEHP exposure increased male-to-female ratio compared to controls. Prenatal DEHP exposure also increased preantral follicle numbers at PND 21 compared to controls. Further, 22.2% of the 20 μg/kg/day treated animals took longer than 5 days to get pregnant at 3 months and 28.6% of the 750 mg/kg/day treated animals lost some of their pups at 6 months. Thus, prenatal DEHP exposure alters F1 sex ratio, increases preantral follicle numbers, and causes some breeding abnormalities

show abstract

Section: Discussionmentioning

confidence: 99%

Prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP) affects reproductive outcomes in female mice

Niermann

Rattan

Brehm

et al. 2015

Reproductive Toxicology

View full text Add to dashboard Cite

show abstract

“…Moreover, low activities have been reported for the pregnane X receptor (PXR), the estrogen receptor–related receptor (ERR), and the thyroid hormone receptor (TR) ( Mnif et al, 2007 ; Okada et al, 2008 ; Abad et al, 2008 ; Matsushima et al, 2007 ; Moriyama et al, 2002 ; Liu et al, 2010 ). BPA was also reported to inhibit TH signaling but at higher concentrations than those that interact with estrogen receptors ( Fini et al, 2009 ), and to cause increases in levels of uterine heat shock proteins (hsps), mainly hsp90a and glucose-regulated protein (grp) 94 ( Papaconstantinou et al, 2002 ). The fact that BPA, in addition to its effect on estrogen receptors, also interferes with other receptors has been used to argue that “the risk assessment of endocrine disrupting compounds, such as BPA, is hampered by large scientific uncertainties” ( Bondesson et al, 2009 ).…”

Section: What Are the Mechanisms Of Action Of Bpa? Does The Multitudementioning

confidence: 99%

Critical evaluation of key evidence on the human health hazards of exposure to bisphenol A

Hengstler

Foth²,

Gebel

et al. 2011

Critical Reviews in Toxicology

307

168

View full text Add to dashboard Cite

Despite the fact that more than 5000 safety-related studies have been published on bisphenol A (BPA), there seems to be no resolution of the apparently deadlocked controversy as to whether exposure of the general population to BPA causes adverse effects due to its estrogenicity. Therefore, the Advisory Committee of the German Society of Toxicology reviewed the background and cutting-edge topics of this BPA controversy. The current tolerable daily intake value (TDI) of 0.05 mg/kg body weight [bw]/day, derived by the European Food Safety Authority (EFSA), is mainly based on body weight changes in two- and three-generation studies in mice and rats. Recently, these studies and the derivation of the TDI have been criticized. After having carefully considered all arguments, the Committee had to conclude that the criticism was scientifically not justified; moreover, recently published additional data further support the reliability of the two-and three-generation studies demonstrating a lack of estrogen-dependent effects at and below doses on which the current TDI is based. A frequently discussed topic is whether doses below 5 mg/ kg bw/day may cause adverse health effects in laboratory animals. Meanwhile, it has become clear that positive results from some explorative studies have not been confirmed in subsequent studies with higher numbers of animals or a priori defined hypotheses. Particularly relevant are some recent studies with negative outcomes that addressed effects of BPA on the brain, behavior, and the prostate in rodents for extrapolation to the human situation. The Committee came to the conclusion that rodent data can well be used as a basis for human risk evaluation. Currently published conjectures that rats are insensitive to estrogens compared to humans can be refuted. Data from toxicokinetics studies show that the half-life of BPA in adult human subjects is less than 2 hours and BPA is completely recovered in urine as BPA-conjugates. Tissue deconjugation of BPA-glucuronide and -sulfate may occur. Because of the extremely low quantities, it is only of minor relevance for BPA toxicity. Biomonitoring studies have been used to estimate human BPA exposure and show that the daily intake of BPA is far below the TDI for the general population. Further topics addressed in this article include reasons why some studies on BPA are not reproducible; the relevance of oral versus non-oral exposure routes; the degree to which newborns are at higher systemic BPA exposure; increased BPA exposure by infusions in intensive care units; mechanisms of action other than estrogen receptor activation; and the current regulatory status in Europe, as well as in the USA, Canada, Japan, New Zealand, and Australia. Overall, the Committee concluded that the current TDI for BPA is adequately justified and that the available evidence indicates that BPA exposure represents no noteworthy risk to the health of the human population, including newborns and babies.

show abstract

“…There are a few studies that report estrogenic regulation of the heat shock chaperones. 17␤-Estradiol and bisphenol A act via the ER in uterine tissue to increase hsp90 and hsp72 mRNA via PKC (162,163). In the CNS, estrogens and androgens protect neurons from ␤-amyloid toxicity by increasing the levels of hsp70; microinjection of hsp70 blocked the toxicity of added intracellular ␤-amyloid peptide (iamyloid␤1-42) (164), suggesting a role in neuroprotection.…”

Section: A Coupling To Transcription Via Stabilization or Dimerizatimentioning

confidence: 99%

Membrane-Initiated Actions of Estrogens in Neuroendocrinology: Emerging Principles

2007

View full text Add to dashboard Cite

Hormonal ligands for the nuclear receptor superfamily have at least two interacting mechanisms of action: 1) classical transcriptional regulation of target genes (genomic mechanisms); and 2) nongenomic actions that are initiated at the cell membrane, which could impact transcription. Although transcriptional mechanisms are increasingly well understood, membrane-initiated actions of these ligands are incompletely understood. Historically, this has led to a considerable divergence of thought in the molecular endocrine field. We have attempted to uncover principles of hormone action that are relevant to membrane-initiated actions of estrogens. There is evidence that the membrane-limited actions of hormones, particularly estrogens, involve the rapid activation of kinases and the release of calcium. Membrane actions of estrogens, which activate these rapid signaling cascades, can also potentiate nuclear transcription. These signaling cascades may occur in parallel or in series but subsequently converge at the level of modification of transcriptionally relevant molecules such as nuclear receptors and/or coactivators. In addition, other hormones or neurotransmitters may also activate cascades to crosstalk with estrogen receptor-mediated transcription. The idea of synergistic coupling between membrane-initiated and genomic actions of hormones fundamentally revises the paradigms of cell signaling in neuroendocrinology.

show abstract

Increases in mouse uterine heat shock protein levels are a sensitive and specific response to uterotrophic agents.

Cited by 16 publications

References 79 publications

Prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP) affects reproductive outcomes in female mice

Prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP) affects reproductive outcomes in female mice

Critical evaluation of key evidence on the human health hazards of exposure to bisphenol A

Membrane-Initiated Actions of Estrogens in Neuroendocrinology: Emerging Principles

Contact Info

Product

Resources

About