Organizational and activational effects of estrogenic endocrine disrupting chemicals

Silbergeld, Ellen K.; Flaws, Jodi A.; Brown, Ken M.

doi:10.1590/s0102-311x2002000200014

Cited by 17 publications

(10 citation statements)

References 80 publications

(79 reference statements)

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“…During critical periods of development, hormones can alter the differentiation of cells and the organization of organs, whereas in most adult stages hormones induce 'activational' responseswhere the effect is observed only as long as the exposure occurs. 6 cology and endocrinology, this is a relatively new research arena. 7 Even the definition of an endocrine disruptor continues to be debated, [8][9][10] and scientists have expressed great concern over the methods used to determine the endocrine disrupting properties of environmental chemicals, measure EDCs in human tissues and fluids, and understand the range of adverse outcomes that can be induced by these compounds.…”

Section: Introductionmentioning

confidence: 99%

Beyond a means of exposure: a new view of the mother in toxicology research

2015

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Section: Introductionmentioning

confidence: 99%

Beyond a means of exposure: a new view of the mother in toxicology research

2015

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“…The skeleton may be particularly sensitive to exogenous hormones or food components with potential hormonal activity (i.e. soy isoflavones) when endogenous levels of hormones are low (11,12), as occurs during postnatal life and during aging (11). Short-term exposure to estrogen or compounds with estrogen-like activity during early stages of development can have positive effects on bone health at adulthood.…”

Section: Introductionmentioning

confidence: 99%

Neonatal Exposure to Daidzein, Genistein, or the Combination Modulates Bone Development in Female CD-1 Mice

Kaludjerovic

Ward

2009

The Journal of Nutrition

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Neonatal exposure to genistein (GEN), an isoflavone abundant in soy, favorably modulates bone mineral density (BMD) and bone strength in mice at adulthood. The study objective was to determine whether early exposure to a combination of the soy isoflavones daidzein (DAI) and GEN that naturally exists in soy protein-based infant formula results in greater benefits to bone at adulthood than either treatment alone. Male and female CD-1 mice (n = 8-16 pups per group per gender) were randomized to subcutaneous injections of DAI (2 mg x kg body weight(-1) x d(-1)), GEN (5 mg x kg body weight(-1) x d(-1)), DAI+GEN (7 mg x kg body weight(-1) x d(-1)), diethylstilbesterol (DES; positive control) (2 mg x kg body weight(-1) x d(-1)), or control (CON) from postnatal d 1-5 and were studied to 4 mo of age. BMD, biomechanical bone strength, and bone microarchitecture were assessed at the femur and lumbar vertebrae (LV). Females treated with DAI, GEN, DAI+GEN, or DES had greater (P < 0.05) BMD at the LV compared with CON and vertebra in the DAI and DES group were more resistant to compression fractures. Microstructural analyses demonstrated that treatment with DAI and GEN resulted in greater (P < 0.05) trabecular connectivity and trabecular thickness, respectively, than the CON. In conclusion, neonatal exposure to DAI and/or GEN had a positive effect on the skeleton of female mice at adulthood, but, compared with individual treatments, DAI+GEN did not have a greater benefit to bone in females or males.

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“…The developmental stages of life are particularly susceptible to endocrine disruption. , Prepubertal estrogen levels in humans of both sexes are comparatively low, sometimes below the detection limit of available assays, providing little binding competition for circulating estrogen-like compounds at available ERs. There is extensive evidence suggesting that an intense period of exposure to relatively high levels of endocrine active compounds 44 in utero, or during neonatal and postnatal development, potentiates immediate and/or long-term developmental effects .…”

Section: The Double-edged Swordmentioning

confidence: 99%

“…Delayed effects may be imperceptible at the time of exposure, such that they become apparent, or of consequence, only as temporal endocrinologic changes occur during puberty, adulthood, or pregnancy . To demonstrate this phenomenon, Naciff et al used a microarray technique to analyze 8740 genes derived from the uterus and ovary of gestational rats that were transplacentally exposed to genistein and revealed that a treatment effect was immediately evident in 344 genes .…”

Section: The Double-edged Swordmentioning

confidence: 99%

Soy Isoflavones and Bone Health: A Double-Edged Sword?

Reinwald

Weaver

2005

J. Nat. Prod.

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Numerous publications and research studies on isoflavones have prompted a nationwide increase in the consumption of soy-based foods and supplements in the United States. Isoflavones are natural endocrine active compounds generally considered to promote health and prevent or slow the onset of certain chronic diseases such as osteoporosis. The beneficial effects of soy isoflavones on bone may, however, be life-stage specific and dependent on the estrogen receptor number and endogenous hormone milieu. Perimenopausal and early menopausal women may therefore be more receptive to the therapeutic effects of isoflavones on bone loss prior to the diminution of estrogen receptors that occurs in the postmenopausal years, whereas laboratory studies in developmental age range animals have demonstrated the potential for adverse effects following exposure to high levels of soy isoflavones. Clinical studies in developing humans that either support or refute findings in animal studies are lacking. The effects of chronic consumption of high levels of soy isoflavones at each life stage to assess risk-benefit ratios should be a high priority of research.

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Organizational and activational effects of estrogenic endocrine disrupting chemicals

Abstract: Endocrine disruption is a hypothesis of common mode of action that may define a set of structurally varied chemicals, both natural and synthetic. Their common mode of action may

Cited by 17 publications

References 80 publications

Beyond a means of exposure: a new view of the mother in toxicology research

Beyond a means of exposure: a new view of the mother in toxicology research

Neonatal Exposure to Daidzein, Genistein, or the Combination Modulates Bone Development in Female CD-1 Mice

Soy Isoflavones and Bone Health: A Double-Edged Sword?

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