Leuprolide Acetate, a GnRH Agonist, Improves the Neurogenic Bowel in Ovariectomized Rats with Spinal Cord Injury

Overview

Journal Dig Dis Sci

Specialty Gastroenterology

Date 2019 Sep 1

PMID 31471861

Citations 2

Authors

Moises Altamira-Camacho

Daniel Medina-Aguinaga

Yolanda Cruz

Denisse Calderon-Vallejo

Kalman Kovacs

Fabio Rotondo

J Luis Quintanar

Affiliations

Soon will be listed here.

Abstract

Background: Electromyographic studies have shown that external anal sphincter activity is modified in response to distension in animals with spinal cord injury. Gonadotropin-releasing hormone and its agonist leuprolide acetate have neurotrophic properties in animals with spinal cord injury.

Aim: This study was to determine the effects of leuprolide acetate treatment on electromyographic activity of the external anal sphincter and anorectal manometry in ovariectomized rats with spinal cord injury.

Methods: Adult ovariectomized rats were divided in three groups: (a) sham of spinal cord injury, (b) spinal cord injury treated with saline solution, and (c) spinal cord injury treated with leuprolide acetate. The spinal cord injury was induced by clamping at level T9. Leuprolide acetate dosage of 10 μg/kg was proctored intramuscular for 5 weeks, commencing the day after the lesion. Electromyography of the external anal sphincter, anorectal manometry, and volume of the cecum were evaluated in all groups.

Results: The electromyographic study of the external anal sphincter activity showed a significant improvement in injured rats treated with leuprolide acetate. Manometric analysis and cecum volume data obtained in animals with leuprolide acetate were very similar to those found in the sham group.

Conclusions: These results demonstrate that leuprolide acetate treatment improves the neurogenic colon in ovariectomized rats with spinal cord injury.

Citing Articles

Gonadotropin-releasing hormone and growth hormone act as anti-inflammatory factors improving sensory recovery in female rats with thoracic spinal cord injury.

Martinez-Moreno C, Calderon-Vallejo D, Diaz-Galindo C, Hernandez-Jasso I, Olivares-Hernandez J, Avila-Mendoza J Front Neurosci. 2023; 17:1164044.

PMID: 37360158 PMC: 10288327. DOI: 10.3389/fnins.2023.1164044.

The roles of GnRH in the human central nervous system.

Wickramasuriya N, Hawkins R, Atwood C, Butler T Horm Behav. 2022; 145:105230.

PMID: 35809386 PMC: 9990468. DOI: 10.1016/j.yhbeh.2022.105230.

References

Mathias J, Clench M, Abell T, Koch K, Lehman G, Robinson M . Effect of leuprolide acetate in treatment of abdominal pain and nausea in premenopausal women with functional bowel disease: a double-blind, placebo-controlled, randomized study. Dig Dis Sci. 1998; 43(6):1347-55. DOI: 10.1023/a:1018888631286. View

Mathias J, Ferguson K, Clench M . Debilitating "functional" bowel disease controlled by leuprolide acetate, gonadotropin-releasing hormone (GnRH) analog. Dig Dis Sci. 1989; 34(5):761-6. DOI: 10.1007/BF01540350. View

Krassioukov A, Eng J, Claxton G, Sakakibara B, Shum S . Neurogenic bowel management after spinal cord injury: a systematic review of the evidence. Spinal Cord. 2010; 48(10):718-33. PMC: 3118252. DOI: 10.1038/sc.2010.14. View

Quintanar J, Salinas E, Gonzalez R . Gonadotropin-releasing hormone receptor in spinal cord neurons of embryos and adult rats. Neurosci Lett. 2009; 461(1):21-4. DOI: 10.1016/j.neulet.2009.06.028. View

Ohlsson B . Gonadotropin-Releasing Hormone and Its Role in the Enteric Nervous System. Front Endocrinol (Lausanne). 2017; 8:110. PMC: 5461264. DOI: 10.3389/fendo.2017.00110. View

Basso D, Beattie M, Bresnahan J . A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 1995; 12(1):1-21. DOI: 10.1089/neu.1995.12.1. View

Okada H, Doken Y, Ogawa Y . Persistent suppression of the pituitary-gonadal system in female rats by three-month depot injectable microspheres of leuprorelin acetate. J Pharm Sci. 1996; 85(10):1044-8. DOI: 10.1021/js960123a. View

Periti P, Mazzei T, Mini E . Clinical pharmacokinetics of depot leuprorelin. Clin Pharmacokinet. 2002; 41(7):485-504. DOI: 10.2165/00003088-200241070-00003. View

Calderon-Vallejo D, Quintanar J . Gonadotropin-releasing hormone treatment improves locomotor activity, urinary function and neurofilament protein expression after spinal cord injury in ovariectomized rats. Neurosci Lett. 2012; 515(2):187-90. DOI: 10.1016/j.neulet.2012.03.052. View

10.

Quintanar J, Salinas E . Neurotrophic effects of GnRH on neurite outgrowth and neurofilament protein expression in cultured cerebral cortical neurons of rat embryos. Neurochem Res. 2007; 33(6):1051-6. DOI: 10.1007/s11064-007-9549-9. View

11.

Mathias J, Clench M, Roberts P . Effect of leuprolide acetate in patients with functional bowel disease. Long-term follow-up after double-blind, placebo-controlled study. Dig Dis Sci. 1994; 39(6):1163-70. DOI: 10.1007/BF02093779. View

12.

Medina-Aguinaga D, Munoz A, Luna M, Martinez-Moreno C, Quintanar-Stephano A, Quintanar J . Administration of leuprolide acetate, a GnRH agonist, improves urodynamic parameters in ovariectomized rats. Neurourol Urodyn. 2018; 37(5):1574-1582. DOI: 10.1002/nau.23505. View

13.

Poon P, Gupta D, Shoichet M, Tator C . Clip compression model is useful for thoracic spinal cord injuries: histologic and functional correlates. Spine (Phila Pa 1976). 2008; 32(25):2853-9. DOI: 10.1097/BRS.0b013e31815b7e6b. View

14.

Quintanar J, Calderon-Vallejo D, Hernandez-Jasso I . Effects of GnRH on Neurite Outgrowth, Neurofilament and Spinophilin Proteins Expression in Cultured Spinal Cord Neurons of Rat Embryos. Neurochem Res. 2016; 41(10):2693-2698. DOI: 10.1007/s11064-016-1983-0. View

15.

Quintanar J, Salinas E, Gonzalez R . Expression of gonadotropin-releasing hormone receptor in cerebral cortical neurons of embryos and adult rats. Neurosci Lett. 2006; 411(1):22-5. DOI: 10.1016/j.neulet.2006.06.077. View

16.

Huang W, Yao B, Sun L, Pu R, Wang L, Zhang R . Immunohistochemical and in situ hybridization studies of gonadotropin releasing hormone (GnRH) and its receptor in rat digestive tract. Life Sci. 2001; 68(15):1727-34. DOI: 10.1016/s0024-3205(01)00968-7. View

17.

Lynch A, Anthony A, Dobbs B, Frizelle F . Anorectal physiology following spinal cord injury. Spinal Cord. 2000; 38(10):573-80. DOI: 10.1038/sj.sc.3101076. View

18.

Valles M, Vidal J, Clave P, Mearin F . Bowel dysfunction in patients with motor complete spinal cord injury: clinical, neurological, and pathophysiological associations. Am J Gastroenterol. 2006; 101(10):2290-9. DOI: 10.1111/j.1572-0241.2006.00729.x. View

19.

Valles M, Mearin F . [Intestinal alterations in patients with a medullary lesion]. Gastroenterol Hepatol. 2012; 35(5):330-6. DOI: 10.1016/j.gastrohep.2011.11.014. View

20.

Holmes G, Van Meter M, Beattie M, Bresnahan J . Serotonergic fiber sprouting to external anal sphincter motoneurons after spinal cord contusion. Exp Neurol. 2005; 193(1):29-42. DOI: 10.1016/j.expneurol.2005.01.002. View