Elin Sand1, Ulrikke Voss2, Bodil Ohlsson3, Eva Ekblad4. 1. Department of Experimental Medical Science, Unit Neurogastroenterology, BMC B11, Lund University, Sölvegatan 19, SE 22184 Lund, Sweden. Electronic address: elin.sand@med.lu.se. 2. Department of Experimental Medical Science, Unit Neurogastroenterology, BMC B11, Lund University, Sölvegatan 19, SE 22184 Lund, Sweden. Electronic address: ulrikke.voss@med.lu.se. 3. Department of Clinical Sciences, Division of Internal Medicine, Lund University, Sweden Lund University, Inga Marie Nilssons gata 32, SE 21428 Malmö, Sweden. Electronic address: bodil.ohlsson@med.lu.se. 4. Department of Experimental Medical Science, Unit Neurogastroenterology, BMC B11, Lund University, Sölvegatan 19, SE 22184 Lund, Sweden. Electronic address: eva.ekblad@med.lu.se.
Abstract
BACKGROUND: Clinical observations have suggested repeated gonadotropin-releasing hormone (GnRH) exposure to cause intestinal dysfunction and loss of enteric neurons. This has been further studied and confirmed in a rat in vivo model involving iterated GnRH treatments. Mechanisms behind are enigmatic since no GnRH receptors are found to be expressed in enteric neurons neither in man nor rat. Both species, however, harbor substantial subpopulations of luteinizing hormone (LH) receptor-immunoreactive myenteric neurons which suggests that intestinal GnRH-induced neuropathy may be mediated by LH release. AIMS: To reveal if exposures of GnRH or LH to rat myenteric neurons in vitro cause neuronal loss. METHODS: Primary cultured adult rat myenteric neurons were exposed to single or repeated treatments of the GnRH analog buserelin or the LH analog lutrotropin alpha, and neuronal survival was determined by cell counting. Possible presence of GnRH- or LH receptor -immunoreactive neurons was determined by immunocytochemistry. RESULTS: Exposure to the LH, but not the GnRH, analog caused significantly reduced neuronal survival. LH, but not GnRH, receptors were found to be expressed on cultured myenteric neurons. CONCLUSION: Myenteric neurons express LH receptors in vitro and LH exposure causes reduced neuronal survival. This suggests that GnRH-induced enteric neuropathy in vivo is mediated by way of LH release and activation of enteric neuronal LH receptors.
BACKGROUND: Clinical observations have suggested repeated gonadotropin-releasing hormone (GnRH) exposure to cause intestinal dysfunction and loss of enteric neurons. This has been further studied and confirmed in a rat in vivo model involving iterated GnRH treatments. Mechanisms behind are enigmatic since no GnRH receptors are found to be expressed in enteric neurons neither in man nor rat. Both species, however, harbor substantial subpopulations of luteinizing hormone (LH) receptor-immunoreactive myenteric neurons which suggests that intestinal GnRH-induced neuropathy may be mediated by LH release. AIMS: To reveal if exposures of GnRH or LH to rat myenteric neurons in vitro cause neuronal loss. METHODS: Primary cultured adult rat myenteric neurons were exposed to single or repeated treatments of the GnRH analog buserelin or the LH analog lutrotropin alpha, and neuronal survival was determined by cell counting. Possible presence of GnRH- or LH receptor -immunoreactive neurons was determined by immunocytochemistry. RESULTS: Exposure to the LH, but not the GnRH, analog caused significantly reduced neuronal survival. LH, but not GnRH, receptors were found to be expressed on cultured myenteric neurons. CONCLUSION: Myenteric neurons express LH receptors in vitro and LH exposure causes reduced neuronal survival. This suggests that GnRH-induced enteric neuropathy in vivo is mediated by way of LH release and activation of enteric neuronal LH receptors.
Entities:
Keywords:
Enteric nervous system (ENS); Gonadotropin-releasing hormone (GnRH); Luteinizing hormone; Primary cultures of enteric neurons