Sıçan Beyninde Vanilloid Resptör Altgrup Tip-1’in Gonodotropin Salgılayan Hormon Nöronlarında Ifade Edilmesi

Year 2020, , 331 - 336, 01.09.2020

Şehime G Temel

https://doi.org/10.17343/sdutfd.623659

Abstract

Kapsisum biberlerinde
bulunan ve ısı hissini üreten lipofilik bir vanilloid madde olan Kapsaisin
(KAP), birincil afferent nöronlar üzerinde belirgin bir uyarıcı etkiye sahiptir
ve uzun zamandan beri sensitif nöronları tanımlamak için nöroparmakolojik bir
araç olarak kullanılmaktadır. Kapsaisin etkisini Vanilloid Reseptör Alt Tür-Tip
1 (VR1) ile gösterir. Kapsaisin, çeşitli beyin bölgelerini etkiler, beyinde
vanillod duyarlı nöronların var olduğu çeşitli çalışmalarda bildirilmiştir.
Hipotalamusta bulunan VR1 reseptörleri büyük olasılıkla ağrı vücut ısısının
düzenlenmesi, besin alımı, metabolik denge vb. diğer önemli fonksiyonlara
sahiptir. Bu çalışmada, VR1 reseptörlerinin üreme üzerindeki potansiyel
fizyolojik rolünü araştırmayı amaçladık. Bu amaç ile sıçan beyninde VR1 ifade
eden Gonodotropin Salgılayan Hormonu (GnRH) nöronlarının dağılımını araştırmak
için ikili immünoflöresan tekniğini kullandık. Çoğu VR1 pozitif GnRH nöronu
ağırlıklı olarak organ vascualris lamina terminalinde bulunur ve preoptik alan
daha az medial septum diyagonal bandında uzanır. VR1'in GnRH nöronlarında ifade
edilmesi önemlidir, bu bulgu VR1’in üreme aksında rol oynayabileceğini
gösterebilir.

Keywords

GnRH, VR-1, Ko-lokalizasyon

Project Number

-

The Expression of Vanilloid Receptor Subtype-1 (VR1) in Gonadotropin-Releasing Hormone in Rat Brain

Abstract

Capsaicine (CAP), a lipophilic vanilloid substance found in Capsicum peppers which produces the sensation of heat, has a prominent excitatory action on primary afferent neurons, and has long been used as a neuropharmacological tool to identify sensitive neurons. CAP shows its effect via Vanilloid Receptor Subtype-1 (VR1). Capsaicin affects a variety of brain regions , the presence of vanillod sensitive neurons in the brain has been reported in several studies. The VR1 receptors present in the hypothalamus most likely have other important functions including regulation of body temperature, food intake, metabolic balance etc. In this study we aimed to investigate potential physiological role of VR1 receptors in reproduction. Fort his purpose we performed dual immunofluorescence staining to explore the distribution of Gonodotropin Releasing Hormone (GnRH) neurons that express VR1 in rat brain. Most VR1 positive GnRH neurons found predominantly in organum vascularis lamina terminalis and preoptic area lesser extend in medial septum diagonal band. The findings that VR1 is expressed in GnRH neurons is of great importance, it can be speculated that VR1 may have a role in reproductive axis.

Keywords

GnRH, VR1, Co-Localization

Supporting Institution

-

Project Number

-

Thanks

We thank especially Prof. Dr. Aytekin Özer, Dr. Ş Canan Mızrak- Van Grinsven for their valuable conceptual contributions to the origin of this study, wet lab and VR1 antibody, and Drs. Alp Can for Confocal Microscopy Facility (Ankara University, College of Medicine, Dept. of Histology and Embryology) and Lothar Jennes for GnRH antibody (Retured Faculty member of University of Kentucky, College of Medicine, Dept. of Anatomy and Neurobiology) overall for their generous help and support on this study.

References

• 1. Tominaga M, Julius D. Capsaicin receptor in the pain pathway. Jpn J Pharmacol 2000. doi:10.1254/jjp.83.20.
• 2. Szallasi A, Blumberg PM. Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol Rev 1999.
• 3. Mezey E, Tóth ZE, Cortright DN, Arzubi MK, Krause JE, Elde R, Guo A, Blumberg PM, Szallasi A. Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-likeimmunoreactivity, in the central nervous system of the rat and human. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3655-60.
• 4. Tóth A, Boczán J, Kedei N, Lizanecz E, Bagi Z, Papp Z, et al. Expression and distribution of vanilloid receptor 1 (TRPV1) in the adult rat brain. Mol Brain Res2005. doi:10.1016/j.molbrainres.2004.12.003.
• 5. Marinelli S, Vaughan CW, Christie MJ, Connor M. Capsaicin activation of glutamatergic synaptic transmission in the rat locus coeruleus in vitro. J Physiol 2002. doi:10.1113/jphysiol.2002.022863.
• 6. Bobyntsev II, Sever’yanova LA, Kryukov AA. Effect of gonadotropin-releasing hormone analogue on thermal nociception in mice. Bull Exp Biol Med 2006. doi:10.1007/s10517-006-0125-0.
• 7. Bradshaw HB, Temple JL, Wood E, Berkley KJ. Estrous variations in behavioral responses to vaginal and uterine distention in the rat. Pain 1999. doi:10.1016/S0304-3959(99)00049-4.
• 8. Fillingim RB, Edwards RR. The association of hormone replacement therapy with experimental pain responses in postmenopausal women. Pain 2001. doi:10.1016/S0304-3959(01)00256-1.
• 9. Liu B, Eisenach JC, Tong C. Chronic estrogen sensitizes a subset of mechanosensitive afferents innervating the uterine cervix. J Neurophysiol 2005. doi:10.1152/jn.01012.2004.
• 10. Dwight M.N, Timothy E.K, Patricia W. N. Neuroendocrine and behavioral effects of intrathecal capsaicin in adult female rats. Brain Research BulletinVolume 18, Issue 1, January 1987, Pages 109-114. DOI: 10.1016/0361-9230(87)90038-4
• 11. Melekoglu R, Ciftci O, Eraslan S, Cetin A, Basak N . Beneficial effects of curcumin and capsaicin on cyclophosphamide-induced premature ovarian failure in a rat model. J Ovarian Res. 2018 Apr 26;11(1):33. doi: 10.1186/s13048-018-0409-9.
• 12. Krisztina Pohoczky, Jozsef Kun, Balint Szalontai, Eva Szoke, Eva Saghy, Maja Payrits, Bela Kajtar, Krisztina Kovacs, Jozsef Laszlo Kornyei, Janos Garai,Andras Garami, Aniko Perkecz, Levente Czeglediand Zsuzsanna Helyes. Estrogen-dependent up-regulation of TRPA1 and TRPV1 receptor proteins in the rat endometrium.Journal of Molecular (2016) 56, 135–149.DOI: 10.1530/JME-15-0184.
• 13. Mizrak SC, Gadella BM, Erdost H, Ozer A, van Pelt AMM, van Dissel-Emiliani FMF. Spermatogonial stem cell sensitivity to capsaicin: An in vitro study. Reprod Biol Endocrinol 2008. doi:10.1186/1477-7827-6-52.
• 14. Mizrak SC, van Dissel-Emiliani FMF. Transient receptor potential vanilloid receptor-1 confers heat resistance to male germ cells. Fertil Steril 2008. doi:10.1016/j.fertnstert.2007.10.081.
• 15. Oláh M, Milloh H, Wenger T. The role of endocannabinoids in the regulation of luteinizing hormone and prolactin release. Differences between the effects of AEA and 2AG. Mol Cell Endocrinol 2008. doi:10.1016/j.mce.2008.01.005.
• 16. Spies HG, Norman RL. Interaction of estradiol and lhrh on lh release in rhesus females: Evidence for a neural site of action. Endocrinology 1975. doi:10.1210/endo-97-3-685.
• 17. Levine JE, Norman RL, Gliessman PM, Oyama TT, Bangsberg DR, Spies HG. In vivo gonadotropin-releasing hormone release and serum luteinizing hormone measurements in ovariectomized, estrogen-treated rhesus macaques. Endocrinology 1985. doi:10.1210/endo-117-2-711.
• 18. Li DP, Chen SR, Pan HL. VR1 receptor activation induces glutamate release and postsynaptic firing in the paraventricular nucleus. J Neurophysiol 2004. doi:10.1152/jn.00171.2004.
• 19. Birder L.A., Kanai A.J., De Groat W.C., Kiss S., Nealen M.L., Burke N.E., Dineley K.E.: Vanilloid Receptor expression suggests a sensory role for urinary bladder epithelial cells. Proc. Natl. Acad. Sci. USA, 2001, 98, 13396-13401. DOI: 10.1073/pnas.231243698.
• 20. Ständer S., Moormann C., Schumacher M., Buddenkotte J., Artuc M., Shpacovitch V., Brzoska T.: Expression of vanilloid receptor subtype 1 in cutaneous sensory nerve fibers, mast cells, and epithelial cells of appendage structures. Exp. Dermatol., 2004, 13, 129-139. DOI: 10.1111/j.0906-6705.2004.0178.x.