The Experts below are selected from a list of 1773 Experts worldwide ranked by ideXlab platform
Hubertus Jarry - One of the best experts on this subject based on the ideXlab platform.
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comparative analysis of different puberty inhibiting mechanisms of two gnrh agonists and the gnrh antagonist cetrorelix using a female rat model
Pediatric Research, 2000Co-Authors: Christian L. Roth, Heike Luft, Christoph Seidel, Sabine Leonhardt, Wolfgang Wuttke, Hubertus JarryAbstract:GnRH agonists are the established treatment of precocious puberty caused by premature stimulation of gonadotropin secretion. It has been reported that after an initial stimulation (“flare-up”) they reduce LH secretion by desensitization of pituitary GnRH receptors. Little has been published about the use of GnRH antagonists such as cetrorelix to control the onset of puberty and whether they are potentially advantageous compared with GnRH agonists. We conducted two multigroup experiments (12 and 10 d, respectively) treating prepubertal/peripubertal female rats with either the GnRH agonist triptorelin or Buserelin and compared them with rats treated with the GnRH antagonist cetrorelix and controls to assess the effects on pubertal progress and serum hormones. In the second experiment, the effects of Buserelin and cetrorelix on gene expression of the GnRH receptor, LH-β, FSH-β, and the alpha subunit genes in the pituitary were also investigated. Cetrorelix, triptorelin, and Buserelin retarded the onset of puberty as determined by delayed vaginal opening, lower ovarian weights, and lower serum estradiol levels. However, although LH and FSH levels were stimulated by both agonists, they were inhibited by cetrorelix. In the cetrorelix versus Buserelin experiment, pituitary gene expression of the GnRH receptor and LH-β subunit were significantly lower in cetrorelix treated rats compared with controls whereas Buserelin had little effect. Expression of FSH-β and alpha subunit were stimulated by Buserelin but not by cetrorelix. Even though all three of these GnRH analogues inhibited gonadal development and delayed the onset of puberty , the GnRH agonists had stimulating and inhibiting effects on the pituitary-gonadal axis whereas cetrorelix exerted only inhibiting effects. We conclude from this female rat model that cetrorelix may offer advantages for a more controlled medical treatment of precocious puberty compared with GnRH agonist treatment.
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comparative analysis of different puberty inhibiting mechanisms of two gnrh agonists and the gnrh antagonist cetrorelix using a female rat model
Pediatric Research, 2000Co-Authors: Christian L. Roth, Heike Luft, Christoph Seidel, Sabine Leonhardt, Wolfgang Wuttke, Hubertus JarryAbstract:GnRH agonists are the established treatment of precocious puberty caused by premature stimulation of gonadotropin secretion. It has been reported that after an initial stimulation ("flare-up") they reduce LH secretion by desensitization of pituitary GnRH receptors. Little has been published about the use of GnRH antagonists such as cetrorelix to control the onset of puberty and whether they are potentially advantageous compared with GnRH agonists. We conducted two multigroup experiments (12 and 10 d, respectively) treating prepubertal/peripubertal female rats with either the GnRH agonist triptorelin or Buserelin and compared them with rats treated with the GnRH antagonist cetrorelix and controls to assess the effects on pubertal progress and serum hormones. In the second experiment, the effects of Buserelin and cetrorelix on gene expression of the GnRH receptor, LH-beta, FSH-beta, and the alpha subunit genes in the pituitary were also investigated. Cetrorelix, triptorelin, and Buserelin retarded the onset of puberty as determined by delayed vaginal opening, lower ovarian weights, and lower serum estradiol levels. However, although LH and FSH levels were stimulated by both agonists, they were inhibited by cetrorelix. In the cetrorelix versus Buserelin experiment, pituitary gene expression of the GnRH receptor and LH-beta subunit were significantly lower in cetrorelix treated rats compared with controls whereas Buserelin had little effect. Expression of FSH-beta and alpha subunit were stimulated by Buserelin but not by cetrorelix. Even though all three of these GnRH analogues inhibited gonadal development and delayed the onset of puberty, the GnRH agonists had stimulating and inhibiting effects on the pituitary-gonadal axis whereas cetrorelix exerted only inhibiting effects. We conclude from this female rat model that cetrorelix may offer advantages for a more controlled medical treatment of precocious puberty compared with GnRH agonist treatment.
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evidence to suggest that gonadotropin releasing hormone inhibits its own secretion by affecting hypothalamic amino acid neurotransmitter release
Neuroendocrinology, 1996Co-Authors: Carlos Feleder, Hubertus Jarry, Sabine Leonhardt, J A Moguilevsky, Wolfgang WuttkeAbstract:The mediobasal hypothalamus of rats contains gonadotropin-releasing hormone (GnRH) receptors. These hypothalamic neurons also express the GnRH corresponding gene. Under these circumstances, the possibility exists that these GnRH receptors could be localized in other neurons, which are GnRH-receptive, unknowing the neurotransmitter quality. Therefore, we studied the in vitro effects of the GnRH agonist Buserelin on GnRH, glutamate, γ-amino-butyric acid (GABA) and taurine release from explanted superfused hypothalami of untreated and Buserelin-pretreated (down-regulated) male rats. When Buserelin was added to the superfusion medium it inhibited promptly the release of GnRH and the excitatory amino acid neurotransmitter glutamate, but stimulated the release of the inhibitory neurotransmitters, GABA and taurine. Hypothalamic release of GnRH from hypothalami collected from Buserelin-treated (30 µg/100 g b.w. twice daily for 4 days) male rats released significantly less GnRH, glutamate and more GABA and taurine. The inhibitory effect of Buserelin was maintained when the superfusion medium continuously contained the GnRH analog. When superfusion of hypothalami from Buserelin-pretreated animals was performed in the absence of Buserelin, GnRH and glutamate release increased significantly within 45–60 min, whereas GABA and taurine release decreased at this time point. When Buserelin was added to the superfusion medium 2 h after Buserelin-free superfusion, GnRH and glutamate release decreased whereas GABA and taurine release increased instantaneously. Buserelin-treated rats showed significantly low values of LH and testosterone than the untreated rats. These results suggest that GnRH receptors may not only be present in GnRH axon terminals in the median eminence, but also on glutamatergic, GABAergic and taurinergic neurons by which GnRH may exert an autoinhibitory ultrashort loop feedback on its own secretion. This effect appears to be connected with glutamatergic, GABAergic and taurinergic neurons.
Bodil Ohlsson - One of the best experts on this subject based on the ideXlab platform.
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long term follow up of Buserelin induced enteric neuropathy in rats
Molecular Medicine Reports, 2016Co-Authors: Anette Jonsson, Elin Sand, Eva Ekblad, Bodil OhlssonAbstract:A few patients have been shown to develop severe abdominal pain and gastrointestinal dysmotility during treatment with gonadotropin‑releasing hormone (GnRH) analogs. A rat model of enteric neuropathy has been developed by administration of the GnRH analog Buserelin to rats. Loss of enteric neurons and ganglioneuritis throughout the gastrointestinal tract has been described, without other histopathological changes. The aim of the present study was to investigate the long‑term effects of this rat model on body weight, and on morphology and inflammatory changes in the gastrointestinal tract. Rats were administered subcutaneous injections of Buserelin or saline once daily for 5 days and allowed to recover for 3 weeks. This regimen was repeated four times. The rats were weighed weekly and were sacrificed 16 weeks after the fourth treatment. The bowel wall was measured by morphometry, and the presence of enteric neurons, mast cells, eosinophils and T‑lymphocytes was evaluated. Buserelin‑treated rats were shown to have a lower body weight at sacrifice, as compared with the controls (P<0.05). Compared with controls, Buserelin treatment caused loss of myenteric neurons in the ileum and colon (P<0.01), a thinner circular muscle layer in ileum (P<0.05) and longitudinal muscle layer in colon (P<0.05), increased number of eosinophils in the submucosa of the ileum (P<0.05), and an increased number of T‑lymphocytes in the submucosa and circular muscle layer of the fundus (P<0.01 and P<0.05, respectively) and circular muscle layer of the colon (P<0.05). Mast cells were equally distributed in the two groups. Thus, long‑term follow‑up of Buserelin‑induced enteric neuropathy reveals reduced body weight, loss of myenteric neurons, thinning of muscle layers, and increased numbers of eosinophils and T‑lymphocytes in the gastrointestinal tract.
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Buserelin treatment to rats causes enteric neurodegeneration with moderate effects on crf immunoreactive neurons and enterobacteriaceae in colon and in acetylcholine mediated permeability in ileum
BMC Research Notes, 2015Co-Authors: Elin Sand, Eva Ekblad, Caroline Linninge, Liudmyla Lozinska, Emil Egecioglu, Bodil Roth, Goran Molin, Bjorn Westrom, Bodil OhlssonAbstract:The gonadotropin-releasing hormone (GnRH) analog Buserelin causes enteric neuronal loss. Acute stress or injection of corticotropin-releasing factor (CRF) affects motility, secretion, and barrier function of the gastrointestinal tract. The aim of the study was to characterize the CRF immunoreactivity in enteric neurons after Buserelin treatment, and to evaluate possible effects of enteric neuropathy on gut microbiota, intestinal permeability, and stress response behavior. Sixty rats were given Buserelin (20 μg) or saline subcutaneously for 5 days, repeated four times with 3 weeks in-between. At the study end, enteric neuronal density, enteric expression of CRF, gut microbial composition, and plasma levels of adrenocorticotropic hormone (ACTH) and CRF were analyzed. Intestinal permeability was examined in Ussing chambers and the reaction to stressful events was measured by behavior tests. Buserelin treatment reduced the number of neurons along the entire gastrointestinal tract, with increased relative numbers of CRF-immunoreactive submucosal and myenteric neurons in colon (p < 0.05 and p < 0.01, respectively). The overall microbial diversity and relative abundance did not differ between groups, but Enterobacteriaceae was decreased in colon in Buserelin-treated rats (p = 0.020). Basal intestinal permeability did not differ between groups, whereas carbachol stimulation increased ileum permeability in controls (p < 0.05), but not in Buserelin-treated rats. Buserelin did not affect stress behavior. Although Buserelin treatment leads to enteric neuronal loss along the gastrointestinal tract with an increased percentage of CRF-immunoreactive neurons in colon, the physiology is well preserved, with modest effects on colon microbiota and absence of carbachol-induced permeability in ileum as the only observed changes.
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Gonadotropin-releasing hormone analog Buserelin causes neuronal loss in rat gastrointestinal tract
Cell and Tissue Research, 2013Co-Authors: Elin Sand, Bodil Ohlsson, Ulrikke Voss, Oskar Hammar, Ragnar Alm, Gunilla Nordin Fredrikson, Eva EkbladAbstract:Gonadotropin-releasing hormone (GnRH) analogs are given to women undergoing in vitro fertilization. Case reports describing the development of chronic intestinal pseudo-obstruction and auto-antibodies against GnRH after such treatment suggest a strong association between intestinal dysfunction and GnRH analogs. No experimental model for studying such a relationship is currently at hand. Our main goal was to investigate possible enteric neurodegeneration and titers of GnRH antibodies in response to repeated administration of the GnRH analog Buserelin in rat. Rats were treated for 1–4 sessions with daily subcutaneous injections of Buserelin or saline for 5 days, followed by 3 weeks of recovery. Buserelin treatment caused significant loss of submucous and myenteric neurons in the fundus, ileum, and colon. The loss of enteric neurons can, at least partly, be explained by increased apoptosis. No GnRH- or GnRH-receptor-immunoreactive (IR) enteric neurons but numerous luteinizing hormone (LH)-receptor-IR neurons were detected. After Buserelin treatment, the relative number of enteric LH-receptor-IR neurons decreased, whereas that of nitric-oxide-synthase-IR neurons increased. No intestinal inflammation or increased levels of circulating interleukins/cytokines were noted in response to Buserelin treatment. Serum GnRH antibody titers were undetectable or extremely low in all rats. Thus, repeated administrations of Buserelin induce neurodegeneration in rat gastrointestinal tract, possibly by way of LH-receptor hyperactivation. The present findings suggest that enteric neurodegenerative effects of GnRH analog treatment in man can be mimicked in rat. However, in contrast to man, no production of GnRH auto-antibodies has been noted in rat.
Wolfgang Wuttke - One of the best experts on this subject based on the ideXlab platform.
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comparative analysis of different puberty inhibiting mechanisms of two gnrh agonists and the gnrh antagonist cetrorelix using a female rat model
Pediatric Research, 2000Co-Authors: Christian L. Roth, Heike Luft, Christoph Seidel, Sabine Leonhardt, Wolfgang Wuttke, Hubertus JarryAbstract:GnRH agonists are the established treatment of precocious puberty caused by premature stimulation of gonadotropin secretion. It has been reported that after an initial stimulation (“flare-up”) they reduce LH secretion by desensitization of pituitary GnRH receptors. Little has been published about the use of GnRH antagonists such as cetrorelix to control the onset of puberty and whether they are potentially advantageous compared with GnRH agonists. We conducted two multigroup experiments (12 and 10 d, respectively) treating prepubertal/peripubertal female rats with either the GnRH agonist triptorelin or Buserelin and compared them with rats treated with the GnRH antagonist cetrorelix and controls to assess the effects on pubertal progress and serum hormones. In the second experiment, the effects of Buserelin and cetrorelix on gene expression of the GnRH receptor, LH-β, FSH-β, and the alpha subunit genes in the pituitary were also investigated. Cetrorelix, triptorelin, and Buserelin retarded the onset of puberty as determined by delayed vaginal opening, lower ovarian weights, and lower serum estradiol levels. However, although LH and FSH levels were stimulated by both agonists, they were inhibited by cetrorelix. In the cetrorelix versus Buserelin experiment, pituitary gene expression of the GnRH receptor and LH-β subunit were significantly lower in cetrorelix treated rats compared with controls whereas Buserelin had little effect. Expression of FSH-β and alpha subunit were stimulated by Buserelin but not by cetrorelix. Even though all three of these GnRH analogues inhibited gonadal development and delayed the onset of puberty , the GnRH agonists had stimulating and inhibiting effects on the pituitary-gonadal axis whereas cetrorelix exerted only inhibiting effects. We conclude from this female rat model that cetrorelix may offer advantages for a more controlled medical treatment of precocious puberty compared with GnRH agonist treatment.
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comparative analysis of different puberty inhibiting mechanisms of two gnrh agonists and the gnrh antagonist cetrorelix using a female rat model
Pediatric Research, 2000Co-Authors: Christian L. Roth, Heike Luft, Christoph Seidel, Sabine Leonhardt, Wolfgang Wuttke, Hubertus JarryAbstract:GnRH agonists are the established treatment of precocious puberty caused by premature stimulation of gonadotropin secretion. It has been reported that after an initial stimulation ("flare-up") they reduce LH secretion by desensitization of pituitary GnRH receptors. Little has been published about the use of GnRH antagonists such as cetrorelix to control the onset of puberty and whether they are potentially advantageous compared with GnRH agonists. We conducted two multigroup experiments (12 and 10 d, respectively) treating prepubertal/peripubertal female rats with either the GnRH agonist triptorelin or Buserelin and compared them with rats treated with the GnRH antagonist cetrorelix and controls to assess the effects on pubertal progress and serum hormones. In the second experiment, the effects of Buserelin and cetrorelix on gene expression of the GnRH receptor, LH-beta, FSH-beta, and the alpha subunit genes in the pituitary were also investigated. Cetrorelix, triptorelin, and Buserelin retarded the onset of puberty as determined by delayed vaginal opening, lower ovarian weights, and lower serum estradiol levels. However, although LH and FSH levels were stimulated by both agonists, they were inhibited by cetrorelix. In the cetrorelix versus Buserelin experiment, pituitary gene expression of the GnRH receptor and LH-beta subunit were significantly lower in cetrorelix treated rats compared with controls whereas Buserelin had little effect. Expression of FSH-beta and alpha subunit were stimulated by Buserelin but not by cetrorelix. Even though all three of these GnRH analogues inhibited gonadal development and delayed the onset of puberty, the GnRH agonists had stimulating and inhibiting effects on the pituitary-gonadal axis whereas cetrorelix exerted only inhibiting effects. We conclude from this female rat model that cetrorelix may offer advantages for a more controlled medical treatment of precocious puberty compared with GnRH agonist treatment.
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evidence to suggest that gonadotropin releasing hormone inhibits its own secretion by affecting hypothalamic amino acid neurotransmitter release
Neuroendocrinology, 1996Co-Authors: Carlos Feleder, Hubertus Jarry, Sabine Leonhardt, J A Moguilevsky, Wolfgang WuttkeAbstract:The mediobasal hypothalamus of rats contains gonadotropin-releasing hormone (GnRH) receptors. These hypothalamic neurons also express the GnRH corresponding gene. Under these circumstances, the possibility exists that these GnRH receptors could be localized in other neurons, which are GnRH-receptive, unknowing the neurotransmitter quality. Therefore, we studied the in vitro effects of the GnRH agonist Buserelin on GnRH, glutamate, γ-amino-butyric acid (GABA) and taurine release from explanted superfused hypothalami of untreated and Buserelin-pretreated (down-regulated) male rats. When Buserelin was added to the superfusion medium it inhibited promptly the release of GnRH and the excitatory amino acid neurotransmitter glutamate, but stimulated the release of the inhibitory neurotransmitters, GABA and taurine. Hypothalamic release of GnRH from hypothalami collected from Buserelin-treated (30 µg/100 g b.w. twice daily for 4 days) male rats released significantly less GnRH, glutamate and more GABA and taurine. The inhibitory effect of Buserelin was maintained when the superfusion medium continuously contained the GnRH analog. When superfusion of hypothalami from Buserelin-pretreated animals was performed in the absence of Buserelin, GnRH and glutamate release increased significantly within 45–60 min, whereas GABA and taurine release decreased at this time point. When Buserelin was added to the superfusion medium 2 h after Buserelin-free superfusion, GnRH and glutamate release decreased whereas GABA and taurine release increased instantaneously. Buserelin-treated rats showed significantly low values of LH and testosterone than the untreated rats. These results suggest that GnRH receptors may not only be present in GnRH axon terminals in the median eminence, but also on glutamatergic, GABAergic and taurinergic neurons by which GnRH may exert an autoinhibitory ultrashort loop feedback on its own secretion. This effect appears to be connected with glutamatergic, GABAergic and taurinergic neurons.
Eva Ekblad - One of the best experts on this subject based on the ideXlab platform.
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long term follow up of Buserelin induced enteric neuropathy in rats
Molecular Medicine Reports, 2016Co-Authors: Anette Jonsson, Elin Sand, Eva Ekblad, Bodil OhlssonAbstract:A few patients have been shown to develop severe abdominal pain and gastrointestinal dysmotility during treatment with gonadotropin‑releasing hormone (GnRH) analogs. A rat model of enteric neuropathy has been developed by administration of the GnRH analog Buserelin to rats. Loss of enteric neurons and ganglioneuritis throughout the gastrointestinal tract has been described, without other histopathological changes. The aim of the present study was to investigate the long‑term effects of this rat model on body weight, and on morphology and inflammatory changes in the gastrointestinal tract. Rats were administered subcutaneous injections of Buserelin or saline once daily for 5 days and allowed to recover for 3 weeks. This regimen was repeated four times. The rats were weighed weekly and were sacrificed 16 weeks after the fourth treatment. The bowel wall was measured by morphometry, and the presence of enteric neurons, mast cells, eosinophils and T‑lymphocytes was evaluated. Buserelin‑treated rats were shown to have a lower body weight at sacrifice, as compared with the controls (P<0.05). Compared with controls, Buserelin treatment caused loss of myenteric neurons in the ileum and colon (P<0.01), a thinner circular muscle layer in ileum (P<0.05) and longitudinal muscle layer in colon (P<0.05), increased number of eosinophils in the submucosa of the ileum (P<0.05), and an increased number of T‑lymphocytes in the submucosa and circular muscle layer of the fundus (P<0.01 and P<0.05, respectively) and circular muscle layer of the colon (P<0.05). Mast cells were equally distributed in the two groups. Thus, long‑term follow‑up of Buserelin‑induced enteric neuropathy reveals reduced body weight, loss of myenteric neurons, thinning of muscle layers, and increased numbers of eosinophils and T‑lymphocytes in the gastrointestinal tract.
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Buserelin treatment to rats causes enteric neurodegeneration with moderate effects on crf immunoreactive neurons and enterobacteriaceae in colon and in acetylcholine mediated permeability in ileum
BMC Research Notes, 2015Co-Authors: Elin Sand, Eva Ekblad, Caroline Linninge, Liudmyla Lozinska, Emil Egecioglu, Bodil Roth, Goran Molin, Bjorn Westrom, Bodil OhlssonAbstract:The gonadotropin-releasing hormone (GnRH) analog Buserelin causes enteric neuronal loss. Acute stress or injection of corticotropin-releasing factor (CRF) affects motility, secretion, and barrier function of the gastrointestinal tract. The aim of the study was to characterize the CRF immunoreactivity in enteric neurons after Buserelin treatment, and to evaluate possible effects of enteric neuropathy on gut microbiota, intestinal permeability, and stress response behavior. Sixty rats were given Buserelin (20 μg) or saline subcutaneously for 5 days, repeated four times with 3 weeks in-between. At the study end, enteric neuronal density, enteric expression of CRF, gut microbial composition, and plasma levels of adrenocorticotropic hormone (ACTH) and CRF were analyzed. Intestinal permeability was examined in Ussing chambers and the reaction to stressful events was measured by behavior tests. Buserelin treatment reduced the number of neurons along the entire gastrointestinal tract, with increased relative numbers of CRF-immunoreactive submucosal and myenteric neurons in colon (p < 0.05 and p < 0.01, respectively). The overall microbial diversity and relative abundance did not differ between groups, but Enterobacteriaceae was decreased in colon in Buserelin-treated rats (p = 0.020). Basal intestinal permeability did not differ between groups, whereas carbachol stimulation increased ileum permeability in controls (p < 0.05), but not in Buserelin-treated rats. Buserelin did not affect stress behavior. Although Buserelin treatment leads to enteric neuronal loss along the gastrointestinal tract with an increased percentage of CRF-immunoreactive neurons in colon, the physiology is well preserved, with modest effects on colon microbiota and absence of carbachol-induced permeability in ileum as the only observed changes.
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Gonadotropin-releasing hormone analog Buserelin causes neuronal loss in rat gastrointestinal tract
Cell and Tissue Research, 2013Co-Authors: Elin Sand, Bodil Ohlsson, Ulrikke Voss, Oskar Hammar, Ragnar Alm, Gunilla Nordin Fredrikson, Eva EkbladAbstract:Gonadotropin-releasing hormone (GnRH) analogs are given to women undergoing in vitro fertilization. Case reports describing the development of chronic intestinal pseudo-obstruction and auto-antibodies against GnRH after such treatment suggest a strong association between intestinal dysfunction and GnRH analogs. No experimental model for studying such a relationship is currently at hand. Our main goal was to investigate possible enteric neurodegeneration and titers of GnRH antibodies in response to repeated administration of the GnRH analog Buserelin in rat. Rats were treated for 1–4 sessions with daily subcutaneous injections of Buserelin or saline for 5 days, followed by 3 weeks of recovery. Buserelin treatment caused significant loss of submucous and myenteric neurons in the fundus, ileum, and colon. The loss of enteric neurons can, at least partly, be explained by increased apoptosis. No GnRH- or GnRH-receptor-immunoreactive (IR) enteric neurons but numerous luteinizing hormone (LH)-receptor-IR neurons were detected. After Buserelin treatment, the relative number of enteric LH-receptor-IR neurons decreased, whereas that of nitric-oxide-synthase-IR neurons increased. No intestinal inflammation or increased levels of circulating interleukins/cytokines were noted in response to Buserelin treatment. Serum GnRH antibody titers were undetectable or extremely low in all rats. Thus, repeated administrations of Buserelin induce neurodegeneration in rat gastrointestinal tract, possibly by way of LH-receptor hyperactivation. The present findings suggest that enteric neurodegenerative effects of GnRH analog treatment in man can be mimicked in rat. However, in contrast to man, no production of GnRH auto-antibodies has been noted in rat.
Elin Sand - One of the best experts on this subject based on the ideXlab platform.
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long term follow up of Buserelin induced enteric neuropathy in rats
Molecular Medicine Reports, 2016Co-Authors: Anette Jonsson, Elin Sand, Eva Ekblad, Bodil OhlssonAbstract:A few patients have been shown to develop severe abdominal pain and gastrointestinal dysmotility during treatment with gonadotropin‑releasing hormone (GnRH) analogs. A rat model of enteric neuropathy has been developed by administration of the GnRH analog Buserelin to rats. Loss of enteric neurons and ganglioneuritis throughout the gastrointestinal tract has been described, without other histopathological changes. The aim of the present study was to investigate the long‑term effects of this rat model on body weight, and on morphology and inflammatory changes in the gastrointestinal tract. Rats were administered subcutaneous injections of Buserelin or saline once daily for 5 days and allowed to recover for 3 weeks. This regimen was repeated four times. The rats were weighed weekly and were sacrificed 16 weeks after the fourth treatment. The bowel wall was measured by morphometry, and the presence of enteric neurons, mast cells, eosinophils and T‑lymphocytes was evaluated. Buserelin‑treated rats were shown to have a lower body weight at sacrifice, as compared with the controls (P<0.05). Compared with controls, Buserelin treatment caused loss of myenteric neurons in the ileum and colon (P<0.01), a thinner circular muscle layer in ileum (P<0.05) and longitudinal muscle layer in colon (P<0.05), increased number of eosinophils in the submucosa of the ileum (P<0.05), and an increased number of T‑lymphocytes in the submucosa and circular muscle layer of the fundus (P<0.01 and P<0.05, respectively) and circular muscle layer of the colon (P<0.05). Mast cells were equally distributed in the two groups. Thus, long‑term follow‑up of Buserelin‑induced enteric neuropathy reveals reduced body weight, loss of myenteric neurons, thinning of muscle layers, and increased numbers of eosinophils and T‑lymphocytes in the gastrointestinal tract.
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Buserelin treatment to rats causes enteric neurodegeneration with moderate effects on crf immunoreactive neurons and enterobacteriaceae in colon and in acetylcholine mediated permeability in ileum
BMC Research Notes, 2015Co-Authors: Elin Sand, Eva Ekblad, Caroline Linninge, Liudmyla Lozinska, Emil Egecioglu, Bodil Roth, Goran Molin, Bjorn Westrom, Bodil OhlssonAbstract:The gonadotropin-releasing hormone (GnRH) analog Buserelin causes enteric neuronal loss. Acute stress or injection of corticotropin-releasing factor (CRF) affects motility, secretion, and barrier function of the gastrointestinal tract. The aim of the study was to characterize the CRF immunoreactivity in enteric neurons after Buserelin treatment, and to evaluate possible effects of enteric neuropathy on gut microbiota, intestinal permeability, and stress response behavior. Sixty rats were given Buserelin (20 μg) or saline subcutaneously for 5 days, repeated four times with 3 weeks in-between. At the study end, enteric neuronal density, enteric expression of CRF, gut microbial composition, and plasma levels of adrenocorticotropic hormone (ACTH) and CRF were analyzed. Intestinal permeability was examined in Ussing chambers and the reaction to stressful events was measured by behavior tests. Buserelin treatment reduced the number of neurons along the entire gastrointestinal tract, with increased relative numbers of CRF-immunoreactive submucosal and myenteric neurons in colon (p < 0.05 and p < 0.01, respectively). The overall microbial diversity and relative abundance did not differ between groups, but Enterobacteriaceae was decreased in colon in Buserelin-treated rats (p = 0.020). Basal intestinal permeability did not differ between groups, whereas carbachol stimulation increased ileum permeability in controls (p < 0.05), but not in Buserelin-treated rats. Buserelin did not affect stress behavior. Although Buserelin treatment leads to enteric neuronal loss along the gastrointestinal tract with an increased percentage of CRF-immunoreactive neurons in colon, the physiology is well preserved, with modest effects on colon microbiota and absence of carbachol-induced permeability in ileum as the only observed changes.
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Gonadotropin-releasing hormone analog Buserelin causes neuronal loss in rat gastrointestinal tract
Cell and Tissue Research, 2013Co-Authors: Elin Sand, Bodil Ohlsson, Ulrikke Voss, Oskar Hammar, Ragnar Alm, Gunilla Nordin Fredrikson, Eva EkbladAbstract:Gonadotropin-releasing hormone (GnRH) analogs are given to women undergoing in vitro fertilization. Case reports describing the development of chronic intestinal pseudo-obstruction and auto-antibodies against GnRH after such treatment suggest a strong association between intestinal dysfunction and GnRH analogs. No experimental model for studying such a relationship is currently at hand. Our main goal was to investigate possible enteric neurodegeneration and titers of GnRH antibodies in response to repeated administration of the GnRH analog Buserelin in rat. Rats were treated for 1–4 sessions with daily subcutaneous injections of Buserelin or saline for 5 days, followed by 3 weeks of recovery. Buserelin treatment caused significant loss of submucous and myenteric neurons in the fundus, ileum, and colon. The loss of enteric neurons can, at least partly, be explained by increased apoptosis. No GnRH- or GnRH-receptor-immunoreactive (IR) enteric neurons but numerous luteinizing hormone (LH)-receptor-IR neurons were detected. After Buserelin treatment, the relative number of enteric LH-receptor-IR neurons decreased, whereas that of nitric-oxide-synthase-IR neurons increased. No intestinal inflammation or increased levels of circulating interleukins/cytokines were noted in response to Buserelin treatment. Serum GnRH antibody titers were undetectable or extremely low in all rats. Thus, repeated administrations of Buserelin induce neurodegeneration in rat gastrointestinal tract, possibly by way of LH-receptor hyperactivation. The present findings suggest that enteric neurodegenerative effects of GnRH analog treatment in man can be mimicked in rat. However, in contrast to man, no production of GnRH auto-antibodies has been noted in rat.
