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Gonadotropin-releasing hormone analog buserelin causes neuronal loss in rat gastrointestinal tract.

Sand, Elin LU ; Voss, Ulrikke LU ; Hammar, Oskar LU ; Alm, Ragnar LU ; Nordin Fredrikson, Gunilla LU ; Ohlsson, Bodil LU and Ekblad, Eva LU (2013) In Cell and Tissue Research1974-01-01+01:00 351(3). p.521-534
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell and Tissue Research1974-01-01+01:00
volume
351
issue
3
pages
521 - 534
publisher
Springer
external identifiers
  • wos:000315490400016
  • pmid:23254679
  • scopus:84881228133
ISSN
1432-0878
DOI
10.1007/s00441-012-1534-1
language
English
LU publication?
yes
id
915b34b4-a275-4e3a-9ae6-e951739e7424 (old id 3347048)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23254679?dopt=Abstract
date added to LUP
2013-01-02 17:25:16
date last changed
2019-02-20 01:05:48
@article{915b34b4-a275-4e3a-9ae6-e951739e7424,
  abstract     = {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.},
  author       = {Sand, Elin and Voss, Ulrikke and Hammar, Oskar and Alm, Ragnar and Nordin Fredrikson, Gunilla and Ohlsson, Bodil and Ekblad, Eva},
  issn         = {1432-0878},
  language     = {eng},
  number       = {3},
  pages        = {521--534},
  publisher    = {Springer},
  series       = {Cell and Tissue Research1974-01-01+01:00},
  title        = {Gonadotropin-releasing hormone analog buserelin causes neuronal loss in rat gastrointestinal tract.},
  url          = {http://dx.doi.org/10.1007/s00441-012-1534-1},
  volume       = {351},
  year         = {2013},
}