Estrogen receptor-α and -β immunoreactivity and mRNA in neurons of sensory and autonomic ganglia and spinal cord

Papka, Raymond E.; Storey-Workley, Megan E.; Shughrue, Paul J.; Merchenthaler, Istvån; Collins, J.J.; Usip, Sharon; Saunders, Philippa T. K.; Shupnik, Margaret A.

doi:10.1007/s004410100363

Cited by 162 publications

(137 citation statements)

References 110 publications

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“…The gastrointestinal tract is highly innervated, and primary sensory afferents convey information between intestine and central nervous system, adapting nociceptive behavior. Estrogen receptors are widely expressed throughout the sensory processing pathway, including dorsal root ganglia and spinal cord (36,37). Our study showed that BPA induces visceral hypersensitivity to graded intensities of colorectal distension, an effect blocked by ICI 182.780, thus depending on ER binding activity.…”

Section: Discussionmentioning

confidence: 55%

Impact of oral bisphenol A at reference doses on intestinal barrier function and sex differences after perinatal exposure in rats

Braniste¹,

Jouault²,

Gaultier³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

164

111

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Bisphenol A (BPA), a chemical estrogen widely used in the foodpackaging industry and baby bottles, is recovered in human fluids (0.1-10 nM). Recent studies have reported that BPA is hormonally active at low doses, emphasizing the debate of a risk for human health. Estrogen receptors are expressed in the colon, and although the major route of BPA exposure is food, the effects on gut have received no attention. We first examined the endocrine disrupting potency of BPA on colonic paracellular permeability (CPP), experimental colitis, and visceral sensitivity in ovariectomized rats orally exposed to 5 mg/kg/d BPA (i.e., the no observed adverse effect level), 50 μg/kg/d BPA (i.e., tolerable daily intake), or lower doses. BPA dosedependently decreased basal CPP, with a half-maximal inhibitory dose of 5.2 μg/kg/d, 10-fold below the tolerable daily intake. This correlated with an increase in epithelial tight junction sealing, also observed in Caco-2 cells exposed to 10 nM BPA. When ovariectomized rats were fed with BPA at the no observed adverse effect level, the severity of colitis was reduced, whereas the same dose increased pain sensitivity to colorectal stimuli. We then examined the impact of perinatal exposure to BPA on intestinal permeability and inflammatory response in the offspring. In female rats, but not in male rats, perinatal BPA evoked a decrease of CPP in adulthood, whereas the proinflammatory response of colonic mucosa was strengthened. This study first demonstrates that the xenoestrogen BPA at reference doses influences intestinal barrier function and gut nociception. Moreover, perinatal exposure promotes the development of severe inflammation in adult female offspring only.endocrine disruptor | gut permeability | inflammation | pain | estrogen

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Section: Discussionmentioning

confidence: 55%

Impact of oral bisphenol A at reference doses on intestinal barrier function and sex differences after perinatal exposure in rats

Braniste¹,

Jouault²,

Gaultier³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

164

111

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“…The sex differences in the distribution pattern are minor (Burke et al, 2000;Vanderhorst et al, 2005). The other known estrogen receptor, ER, is present in laminae II-III in the spinal cord and trigeminal subnucleus caudalis, as shown in female rats (Papka et al, 2001;Shughrue et al, 1997) but the number of cells is small and the mRNA expression is low. Putative membrane ERs, such as GPR30, are also expressed in the rat spinal dorsal horn and dorsal root ganglia (Brailoiu et al, 2007;Dun et al, 2009;Takanami et al, 2010).…”

Section: The Characteristics Of Spinal Er-neurons and Their Relatiomentioning

confidence: 93%

Estrogenic influences in pain processing

Amandusson

Blomqvist

2013

Frontiers in Neuroendocrinology

111

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Gonadal hormones not only play a pivotal role in reproductive behavior and sexual differentiation, they also contribute to thermoregulation, feeding, memory, neuronal survival, and the perception of somatosensory stimuli. Numerous studies on both animals and human subjects have also demonstrated the potential effects of gonadal hormones, such as estrogens, on pain transmission. These effects most likely involve multiple neuroanatomical circuits as well as diverse neurochemical systems and they therefore need to be evaluated specifically to determine the localization and intrinsic characteristics of the neurons engaged. The aim of this review is to summarize the morphological as well as biochemical evidence in support for gonadal hormone modulation of nociceptive processing, with particular focus on estrogens and spinal cord mechanisms.

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“…6 The nuclei of sensory neurons innervating the uterus are known to express ERs, 15 and ER-dependent signaling modulates a range of processes in peripheral nerves. 29,30 We were, therefore, interested in exploring whether the estrogen-dominated microenvironment could play a role in modulating interactions between macrophages and nerves and what regulatory factors may be involved.…”

Section: E2 Mediates a Two-way Dialogue Between Macrophages And Nervesmentioning

confidence: 99%

“…14 Notably, a proportion of the soma of afferent nerve fibers innervating the uterus and peritoneum is reported to express one or both ERs. 15 Although some studies have analyzed the expression of ERs in macrophages isolated from the peritoneal fluid of women with endometriosis, 16,17 expression of ERs in lesion-resident macrophages has not yet been determined.…”

mentioning

confidence: 99%

Estradiol Is a Critical Mediator of Macrophage-Nerve Cross Talk in Peritoneal Endometriosis

Greaves

Temp

Esnal-Zufiurre

et al. 2015

The American Journal of Pathology

143

121

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Endometriosis occurs in approximately 10% of women and is associated with persistent pelvic pain. It is defined by the presence of endometrial tissue (lesions) outside the uterus, most commonly on the peritoneum. Peripheral neuroinflammation, a process characterized by the infiltration of nerve fibers and macrophages into lesions, plays a pivotal role in endometriosis-associated pain. Our objective was to determine the role of estradiol (E2) in regulating the interaction between macrophages and nerves in peritoneal endometriosis. By using human tissues and a mouse model of endometriosis, we demonstrate that macrophages in lesions recovered from women and mice are immunopositive for estrogen receptor b, with up to 20% being estrogen receptor a positive. In mice, treatment with E2 increased the number of macrophages in lesions as well as concentrations of mRNAs encoded by Csf1, Nt3, and the tyrosine kinase neurotrophin receptor, TrkB. By using in vitro models, we determined that the treatment of rat dorsal root ganglia neurons with E2 increased mRNA concentrations of the chemokine C-C motif ligand 2 that stimulated migration of colony-stimulating factor 1edifferentiated macrophages. Conversely, incubation of colony-stimulating factor 1 macrophages with E2 increased concentrations of brainderived neurotrophic factor and neurotrophin 3, which stimulated neurite outgrowth from ganglia explants. In summary, we demonstrate a key role for E2 in stimulating macrophage-nerve interactions, providing novel evidence that endometriosis is an estrogen-dependent neuroinflammatory disorder. Endometriosis affects 10% of reproductive age women and is associated with persistent pelvic pain. 1 It is defined by the presence of endometrial-like tissue (lesions) found outside the uterus, most commonly on the peritoneum. The mechanisms underlying endometriosis-associated pain are poorly understood, but it has been postulated that estrogen-dependent neuroinflammation may be involved. 2 Notably, the presence of endometrial tissue fragments on the peritoneum elicits an immune response, including recruitment of macrophages, 3 blood vessels, and nerve fibers into the resultant lesions. 4,5 Within the lesions, CD68 þ macrophages have been detected in close association with nerve fibers. 6 Studies investigating macrophage activation and recruitment have revealed that endometriosis-associated macrophages exhibit a phenotype consistent with the alternative end of the macrophage activation spectrum. 7,8 In a mouse model of endometriosis that included cell transfer of polarized macrophages, Bacci et al 7 reported that mice injected with proinflammatory macrophages [macrophage (interferon g)] developed microscopic lesions, but those injected with alternatively activated macrophages [macrophage (IL-4)] developed larger lesions with a well-developed vasculature. Our studies in a mouse model of endometriosis have revealed that macrophages resident in peritoneal lesions can originate from both the peritoneum and the endometrium. 9

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Estrogen receptor-α and -β immunoreactivity and mRNA in neurons of sensory and autonomic ganglia and spinal cord

Cited by 162 publications

References 110 publications

Impact of oral bisphenol A at reference doses on intestinal barrier function and sex differences after perinatal exposure in rats

Impact of oral bisphenol A at reference doses on intestinal barrier function and sex differences after perinatal exposure in rats

Estrogenic influences in pain processing

Estradiol Is a Critical Mediator of Macrophage-Nerve Cross Talk in Peritoneal Endometriosis

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