Gonadotropin-releasing hormone analog buserelin causes neuronal loss in rat gastrointestinal tract.
Author
Summary, in English
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.
Department/s
- Neurogastroenterology
- Internal Medicine - Epidemiology
- Chronic Inflammatory and Degenerative Diseases Research Unit
- Cardiovascular Research - Immunity and Atherosclerosis
- EXODIAB: Excellence of Diabetes Research in Sweden
Publishing year
2013
Language
English
Pages
521-534
Publication/Series
Cell and Tissue Research
Volume
351
Issue
3
Links
Document type
Journal article
Publisher
Springer
Topic
- Cell Biology
Status
Published
Research group
- Neurogastroenterology
- Internal Medicine - Epidemiology
- Chronic Inflammatory and Degenerative Diseases Research Unit
- Cardiovascular Research - Immunity and Atherosclerosis
ISBN/ISSN/Other
- ISSN: 1432-0878