Abstract
The expression of the gonadotrophin-releasing hormone receptor expression on pituitary gonadotrophs in humans is well characterized. In nervous system they have also been found in hippocampi and cerebral cortex. However, gonadotrophin-releasing hormone receptor expression in human spinal cord has not been reported. This study was to analyze the gonadotrophin-releasing hormone receptor expression in human spinal cord by immunohistochemistry, mRNAs by reverse transcriptase polymerase chain reaction, cDNA cloning and Western blot. The results show immunoreactive material to gonadotrophin-releasing hormone receptor in motoneurons of the spinal cord. Further, the study revealed that spinal cord expressed the gonadotrophin-releasing hormone receptor mRNA. The amplicon sequence corresponds to 100% of identity to GenBank. In Western blot, a band of 37 kDa were found in extracts of spinal cord and placenta as a control. In conclusion, human spinal cord expresses gonadotrophin-releasing hormone receptor analyzed through immunohistochemistry, the expression of its mRNA, cloning its cDNA and Western blot analysis. The presence of gonadotrophin-releasing hormone receptor in the spinal cord suggests the possibility of an extrapituitary functional role independent of reproductive system.
References
Bjelobaba I, Stojilkovic SS, Naor Z (2018) Gonadotropin-releasing hormone receptor signaling and functions. Front Endocrinol 9:143. https://doi.org/10.3389/fendo.2018.00143
Limonta P, Marelli MM, Moretti R, Marzagalli M, Fontana F, Maggi R (2018) GnRH in the human female reproductive axis. Vitam Horm 107:27–66. https://doi.org/10.1016/bs.vh.2018.01.003
Janjic MM, Prévide RM, Fletcher PA, Sherman A, Smiljanic K, Abebe D et al (2019) Divergent expression patterns of pituitary gonadotropin subunit and GnRH receptor genes to continuous GnRH in vitro and in vivo. Sci Rep 9:20098. https://doi.org/10.1038/s41598-019-56480-1
Stojilkovic SS, Reinhart J, Catt KJ (1994) Gonadotropin-releasing hormone receptors: structure and signal transduction pathways. Endocr Rev 15:462–499. https://doi.org/10.1210/edrv-15-4-462
Quintanar JL, Salinas E, González R (2007) Expression of gonadotropin-releasing hormone receptor in cerebral cortical neurons of embryos and adult rats. Neurosci Lett 411:22–25. https://doi.org/10.1016/j.neulet.2006.06.077
Albertson AJ, Talbott H, Wang Q, Jensen D, Skinner DC (2008) The gonadotropin-releasing hormone type I receptor is expressed in the mouse cerebellum. Cerebellum Lond Engl 7:379–384. https://doi.org/10.1007/s12311-008-0038-8
Albertson AJ, Navratil A, Mignot M, Dufourny L, Cherrington B, Skinner DC (2008) Immunoreactive GnRH type I receptors in the mouse and sheep brain. J Chem Neuroanat 35:326–333. https://doi.org/10.1016/j.jchemneu.2008.03.004
Badr M, Pelletier G (1987) Characterization and autoradiographic localization of LHRH receptors in the rat brain. Synap 1:567–571. https://doi.org/10.1002/syn.890010609
Jennes L, Eyigor O, Janovick JA, Conn PM (1997) Brain gonadotropin releasing hormone receptors: localization and regulation. Recent Prog Horm Res 52:475–490; discussion 490–491
Dolan S, Evans NP, Richter TA, Nolan AM (2003) Expression of gonadotropin-releasing hormone and gonadotropin-releasing hormone receptor in sheep spinal cord. Neurosci Lett 346:120–122. https://doi.org/10.1016/s0304-3940(03)00594-9
Quintanar JL, Salinas E, González R (2009) Gonadotropin-releasing hormone receptor in spinal cord neurons of embryos and adult rats. Neurosci Lett 461:21–24. https://doi.org/10.1016/j.neulet.2009.06.028
Skinner DC, Albertson AJ, Navratil A, Smith A, Mignot M, Talbott H, Scanlan-Blake N (2009) Effects of gonadotrophin-releasing hormone outside the hypothalamic-pituitary reproductive axis. J Neuroendocrinol 21:282–292. https://doi.org/10.1111/j.1365-2826.2009.01842.x
Chi L, Zhou W, Prikhozhan A, Flanagan C, Davidson JS, Golembo M et al (1993) Cloning and characterization of the human GnRH receptor. Mol Cell Endocrinol 91:R1-6. https://doi.org/10.1016/0303-7207(93)90278-r
Kakar SS, Musgrove LC, Devor DC, Sellers JC, Neill JD (1992) Cloning, sequencing, and expression of human gonadotropin releasing hormone (GnRH) receptor. Biochem Biophys Res Commun 189:289–295. https://doi.org/10.1016/0006-291x(92)91556-6
Currie AJ, Fraser HM, Sharpe RM (1981) Human placental receptors for luteinizing hormone releasing hormone. Biochem Biophys Res Commun 99:332–338. https://doi.org/10.1016/0006-291x(81)91749-6
Choi J-H, Gilks CB, Auersperg N, Leung PCK (2006) Immunolocalization of gonadotropin-releasing hormone (GnRH)-I, GnRH-II, and type I GnRH receptor during follicular development in the human ovary. J Clin Endocrinol Metab 91:4562–4570. https://doi.org/10.1210/jc.2006-1147
Chen A, Ganor Y, Rahimipour S, Ben-Aroya N, Koch Y, Levite M (2002) The neuropeptides GnRH-II and GnRH-I are produced by human T cells and trigger laminin receptor gene expression, adhesion, chemotaxis and homing to specific organs. Nat Med 8:1421–1426. https://doi.org/10.1038/nm1202-801
Cheung LWT, Wong AST (2008) Gonadotropin-releasing hormone: GnRH receptor signaling in extrapituitary tissues. FEBS J 275:5479–5495. https://doi.org/10.1111/j.1742-4658.2008.06677.x
Harrison GS, Wierman ME, Nett TM, Glode LM (2004) Gonadotropin-releasing hormone and its receptor in normal and malignant cells. Endocr Relat Cancer 11:725–748. https://doi.org/10.1677/erc.1.00777
Wilson AC, Salamat MS, Haasl RJ, Roche KM, Karande A, Meethal SV et al (2006) Human neurons express type I GnRH receptor and respond to GnRH I by increasing luteinizing hormone expression. J Endocrinol 191:651–663. https://doi.org/10.1677/joe.1.07047
Quintanar JL, Díaz-Galindo C, Calderón-Vallejo D, Hernández-Jasso I, Rojas F, Medina-Aguiñaga D et al (2018) Neurological improvement in patients with chronic spinal cord injury treated with leuprolide acetate, an agonist of GnRH. Acta Neurobiol Exp 78:352–357
Aguilar-Rojas A, Huerta-Reyes M (2009) Human gonadotropin-releasing hormone receptor-activated cellular functions and signaling pathways in extra-pituitary tissues and cancer cells (Review). Oncol Rep 22:981–990. https://doi.org/10.3892/or_00000525
Chartrel N, Collin F, Huang YS, Montero M, Tonon MC, Goos HJ et al (1998) Characterization and localization of two forms of gonadotropin-releasing hormone (GnRH) in the spinal cord of the frog Rana ridibunda. Cell Tissue Res 293:235–243. https://doi.org/10.1007/s004410051115
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Díaz-Galindo, C., Calderón-Vallejo, D., Hernández-Jasso, I. et al. Gonadotropin-Releasing Hormone Receptor Expression in Human Spinal Cord. Neurochem Res 46, 165–170 (2021). https://doi.org/10.1007/s11064-020-03178-w
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11064-020-03178-w