A Novel Mechanism for Endocrine‐Disrupting Effects of Polychlorinated Biphenyls: Direct Effects on Gonadotropin‐Releasing Hormone Neurones

Gore, Andrea C.; Wu, Tao; Oung, Twethida; Lee, J. B.; Woller, Michael J.

doi:10.1046/j.1365-2826.2002.00845.x

Cited by 73 publications

(31 citation statements)

References 77 publications

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“…Although relatively few studies have been performed, most show effects of endocrine disrupting chemicals, both in vitro and in vivo, on GnRH functional properties. In the hypothalamic GT1-7 GnRH cell line [100], polychlorinated biphenyls [65] and organochlorine pesticides such as methoxychlor and chlorpyrifos [61] have significant effects on GnRH gene expression, GnRH peptide release, and GT1-7 cell morphology. GnRH neurons in vivo are also affected by phytoestrogens such as coumestrol [99,171] and industrial contaminants, fungicides, and pesticides [17,59], as manifested by alterations in pulsatile GnRH/LH release, GnRH gene expression, and GnRH cell numbers.…”

Section: Effects Of Edcs On Hypothalamic Gnrh Neuronsmentioning

confidence: 99%

Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems

Gore¹

2008

Frontiers in Neuroendocrinology

231

122

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The ability of a species to reproduce successfully requires the careful orchestration of developmental processes during critical time points, particularly the late embryonic and early postnatal periods. This article begins with a brief presentation of the evidence for how gonadal steroid hormones exert these imprinting effects upon the morphology of sexually differentiated hypothalamic brain regions, the mechanisms underlying these effects, and their implications in adulthood. Then, I review the evidence that aberrant exposure to hormonally-active substances such as exogenous endocrine-disrupting chemicals (EDCs), may result in improper hypothalamic programming, thereby decreasing reproductive success in adulthood. The field of endocrine disruption has shed new light on the discipline of basic reproductive neuroendocrinology through studies on how early life exposures to EDCs may alter gene expression via non-genomic, epigenetic mechanisms, including DNA methylation and histone acetylation. Importantly, these effects may be transmitted to future generations if the germline is affected via transgenerational, epigenetic actions. By understanding the mechanisms by which natural hormones and xenobiotics affect reproductive neuroendocrine systems, we will gain a better understanding of normal developmental processes, as well as to develop the potential ability to intervene when development is disrupted.

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Section: Effects Of Edcs On Hypothalamic Gnrh Neuronsmentioning

confidence: 99%

Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems

Gore¹

2008

Frontiers in Neuroendocrinology

231

122

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“…They can have estrogenic and antiandrogenic activities. The effects of two PCB mixtures, Aroclor 1221 (A1221) and A1254, were tested on the hypothalamic neuronal GT1-7 cells by Gore et al (2002). A1221 increased GnRH transcript and peptide levels.…”

Section: Poly Chlorinated Biphenyls (Pcbs)mentioning

confidence: 99%

Female sexual maturation and reproduction after prepubertal exposure to estrogens and endocrine disrupting chemicals: A review of rodent and human data

Rasier

Toppari

Parent

et al. 2006

Molecular and Cellular Endocrinology

145

108

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Natural hormones and some synthetic chemicals spread into our surrounding environment share the capacity to interact with hormone action and metabolism. Exposure to such compounds can cause a variety of developmental and reproductive detrimental abnormalities in wildlife species and, potentially, in human. Many experimental and epidemiological data have reported that exposure of the developing fetus or neonate to environmentally relevant concentrations of some among these endocrine disrupters induces morphological, biochemical and/or physiological disorders in brain and reproductive organs, by interfering with the hormone actions. The impact of such exposures on the hypothalamic-pituitary-gonadal axis and subsequent sexual maturation is the subject of the present review. We will highlight epidemiological human studies and the effects of early exposure during gestational, perinatal or postnatal life in female rodents.

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“…PCBs and their metabolites can act at multiple nodes of the neuroendocrine axis: they may serve as hormone mimics (Connor et al, 1997), alter circulating hormone levels (Desaulniers et al, 1999), change patterns of estrous cyclicity (Meerts et al, 2004;Buitenhuis et al, 2004), disrupt hormone metabolism Kester et al, 2000;Yamane et al, 1975), influence endocrine-related and hypothalamic gene expression (Aluru et al, 2004;Bansal et al, 2005;Colciago et al, 2005;Flouriot et al, 1995;Gore et al, 2002;Pravettoni et al, 2005;Salama et al, 2003), interfere with hormone binding proteins (Brouwer and van den Berg, 1986;Chauhan et al, 2000), alter neuronal signaling to endocrine regions of the brain (Khan and Thomas, 2001;Morse et al, 1996;Seegal et al, 1985;Seegal et al, 1990) or indirectly affect steroid receptor availability via molecular crosstalk (Brunnberg et al, 2003;Pearce et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

The effects of prenatal PCBs on adult female paced mating reproductive behaviors in rats

Steinberg

Juenger

Gore

2007

Hormones and Behavior

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Polychlorinated biphenyls (PCBs) are a family of toxicants that persist in measurable quantities in human and wildlife tissues, despite their ban in production in 1977. Some PCB mixtures can act as endocrine disrupting chemicals (EDCs) by mimicking or antagonizing the actions of hormones in the brain and periphery. When exposure to hormonally active substances such as PCBs occurs during vulnerable developmental periods, particularly prenatally or in early postnatal life, they can disrupt sex-specific patterning of the brain, inducing permanent changes that can later be manifested as improper sexual behaviors. Here, we investigated the effects of prenatal exposure to the PCB mixture Aroclor (A) 1221 on adult female reproductive behaviors in a dose-response model in the SpragueDawley rat. Using a paced mating paradigm that permits the female to set the timing of mating and control contact with the male during copulation, we were able to uncover significant differences in female-typical sexual activities in A1221-exposed females. Specifically, A1221 causes significant effects on mating trial pacing, vocalizations, ambulation and the female's likelihood to mate. The results further demonstrate that the intermediate treatment group has the greatest number of disrupted endpoints, suggestive of non-linear dose responses to A1221. These data demonstrate that the behavioral phenotype in adulthood is disrupted by low, ecologically relevant exposures to PCBs, and the results have implications for reproductive success and health in wildlife and women. KeywordsAroclor 1221; Paced mating; PCB; Female reproductive behavior; Endocrine disruption Polychlorinated biphenyls (PCBs) were used in industry as inflammable coolants and lubricants and as components of paints and plastics. Banned in 1977 in response to dawning public awareness of their estrogenic and potentially toxic effects on humans and wildlife, PCBs continue to leach into soil, air and groundwater via retired industrial equipment, and from old factories and buildings. PCBs may have variable degrees of impact depending on which congeners or congener mixtures are involved, the organism's age at exposure, the sex of the individual, the degree of exposure and the availability of compensatory diet or social buffering to counteract those effects. An accurate evaluation of ecologically relevant xenobiotic exposure (Battershill, 1994;Brouwer et al., 1999).The neuroendocrine system serves as an interface between the central nervous system and peripheral endocrine organs, and thus represents a prime target for endocrine disruption by PCBs (Patisaul et al., 2006). PCBs and their metabolites can act at multiple nodes of the neuroendocrine axis: they may serve as hormone mimics (Connor et al., 1997), alter circulating hormone levels (Desaulniers et al., 1999), change patterns of estrous cyclicity (Meerts et al., 2004;Buitenhuis et al., 2004), disrupt hormone metabolism Kester et al., 2000;Yamane et al., 1975), influence endocrine-related and hypothalamic gene expression ...

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A Novel Mechanism for Endocrine‐Disrupting Effects of Polychlorinated Biphenyls: Direct Effects on Gonadotropin‐Releasing Hormone Neurones

Cited by 73 publications

References 77 publications

Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems

Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems

Female sexual maturation and reproduction after prepubertal exposure to estrogens and endocrine disrupting chemicals: A review of rodent and human data

The effects of prenatal PCBs on adult female paced mating reproductive behaviors in rats

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