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16.04.2024 | Original Article

Neuroendocrine modulation by metamizole and indomethacin: investigating the impact on neuronal markers and GnRH release

verfasst von: Erkan Maytalman, Dilara Nemutlu Samur

Erschienen in: Endocrine

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Abstract

Purpose

Some evidence that non-steroidal anti-inflammatory drugs have neuroprotective effects indicates their potential for use in a new field. However, their effects on hormone secretion have yet to be adequately discovered. Therefore, we aimed to evaluate the effects of metamizole and indomethacin on neuronal markers as well as the GnRH expression in the GT1-7 cell line.

Methods

The effects of these drugs on proliferation were evaluated by MTT analysis. The effect of 10–50–250 µM concentrations of the drugs also on the expression of neuronal factors and markers, including NGF, nestin and βIII Tubulin, and additionally GnRH, was determined by the RT-qPCR method.

Results

NGF and nestin mRNA expressions were increased in all concentrations of both metamizole and indomethacin. No changes were detected in βIII Tubulin. While metamizole showed an increase in GnRH mRNA expression, there was no change at 10 and 50 µM concentrations of indomethacin, but a remarkable decrease was observed at 250 µM concentrations.

Conclusions

The results of our study showing an increase in the expression of neuronal factors reveal that metamizole and indomethacin may have possible neuroprotective effects. Moreover, the effects on the GnRH expression appear to be different. Animal models are required to confirm these effects of NSAIDs on neurons.
Literatur
16.
Zurück zum Zitat D. Mizuno, K. Konoha-Mizuno, M. Mori, K. Yamazaki, T. Haneda, H. Koyama, M. Kawahara, An In Vitro System Comprising Immortalized Hypothalamic Neuronal Cells (GT1-7 Cells) for Evaluation of the Neuroendocrine Effects of Essential Oils. Evid. Based Complement Altern. Med 2015, 343942 (2015). https://doi.org/10.1155/2015/343942CrossRef D. Mizuno, K. Konoha-Mizuno, M. Mori, K. Yamazaki, T. Haneda, H. Koyama, M. Kawahara, An In Vitro System Comprising Immortalized Hypothalamic Neuronal Cells (GT1-7 Cells) for Evaluation of the Neuroendocrine Effects of Essential Oils. Evid. Based Complement Altern. Med 2015, 343942 (2015). https://​doi.​org/​10.​1155/​2015/​343942CrossRef
23.
Zurück zum Zitat F. Pimpinelli, E. Redaelli, R. Restano-Cassulini, G. Curia, P. Giacobini, A. Cariboni, E. Wanke, G.P. Bondiolotti, F. Piva, R. Maggi, Depolarization differentially affects the secretory and migratory properties of two cell lines of immortalized luteinizing hormone-releasing hormone (LHRH) neurons. Eur. J. Neurosci. 18(6), 1410–1418 (2003). https://doi.org/10.1046/j.1460-9568.2003.02866.xCrossRefPubMed F. Pimpinelli, E. Redaelli, R. Restano-Cassulini, G. Curia, P. Giacobini, A. Cariboni, E. Wanke, G.P. Bondiolotti, F. Piva, R. Maggi, Depolarization differentially affects the secretory and migratory properties of two cell lines of immortalized luteinizing hormone-releasing hormone (LHRH) neurons. Eur. J. Neurosci. 18(6), 1410–1418 (2003). https://​doi.​org/​10.​1046/​j.​1460-9568.​2003.​02866.​xCrossRefPubMed
26.
Zurück zum Zitat R.G. Romanelli, T. Barni, M. Maggi, M. Luconi, P. Failli, A. Pezzatini, E. Pelo, F. Torricelli, C. Crescioli, P. Ferruzzi, R. Salerno, M. Marini, C.M. Rotella, G.B. Vannelli, Expression and function of gonadotropin-releasing hormone (GnRH) receptor in human olfactory GnRH-secreting neurons: an autocrine GnRH loop underlies neuronal migration. J. Biol. Chem. 279(1), 117–126 (2004). https://doi.org/10.1074/jbc.M307955200CrossRefPubMed R.G. Romanelli, T. Barni, M. Maggi, M. Luconi, P. Failli, A. Pezzatini, E. Pelo, F. Torricelli, C. Crescioli, P. Ferruzzi, R. Salerno, M. Marini, C.M. Rotella, G.B. Vannelli, Expression and function of gonadotropin-releasing hormone (GnRH) receptor in human olfactory GnRH-secreting neurons: an autocrine GnRH loop underlies neuronal migration. J. Biol. Chem. 279(1), 117–126 (2004). https://​doi.​org/​10.​1074/​jbc.​M307955200CrossRefPubMed
28.
Zurück zum Zitat E. Dráberová, L. Del Valle, J. Gordon, V. Marková, B. Smejkalová, L. Bertrand, J.P. de Chadarévian, D.P. Agamanolis, A. Legido, K. Khalili, P. Dráber, C.D. Katsetos, Class III beta-tubulin is constitutively coexpressed with glial fibrillary acidic protein and nestin in midgestational human fetal astrocytes: implications for phenotypic identity. J. Neuropathol. Exp. Neurol. 67(4), 341–354 (2008). https://doi.org/10.1097/NEN.0b013e31816a686dCrossRefPubMed E. Dráberová, L. Del Valle, J. Gordon, V. Marková, B. Smejkalová, L. Bertrand, J.P. de Chadarévian, D.P. Agamanolis, A. Legido, K. Khalili, P. Dráber, C.D. Katsetos, Class III beta-tubulin is constitutively coexpressed with glial fibrillary acidic protein and nestin in midgestational human fetal astrocytes: implications for phenotypic identity. J. Neuropathol. Exp. Neurol. 67(4), 341–354 (2008). https://​doi.​org/​10.​1097/​NEN.​0b013e31816a686d​CrossRefPubMed
29.
Zurück zum Zitat S.A. Malone, G.E. Papadakis, A. Messina, N.E.H. Mimouni, S. Trova, M. Imbernon, C. Allet, I. Cimino, J. Acierno, D. Cassatella, C. Xu, R. Quinton, G. Szinnai, P. Pigny, L. Alonso-Cotchico, L. Masgrau, J.D. Maréchal, V. Prevot, N. Pitteloud, P. Giacobini, Defective AMH signaling disrupts GnRH neuron development and function and contributes to hypogonadotropic hypogonadism. Elife 8, e47198 (2019). https://doi.org/10.7554/eLife.47198CrossRefPubMedPubMedCentral S.A. Malone, G.E. Papadakis, A. Messina, N.E.H. Mimouni, S. Trova, M. Imbernon, C. Allet, I. Cimino, J. Acierno, D. Cassatella, C. Xu, R. Quinton, G. Szinnai, P. Pigny, L. Alonso-Cotchico, L. Masgrau, J.D. Maréchal, V. Prevot, N. Pitteloud, P. Giacobini, Defective AMH signaling disrupts GnRH neuron development and function and contributes to hypogonadotropic hypogonadism. Elife 8, e47198 (2019). https://​doi.​org/​10.​7554/​eLife.​47198CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat E. De Luna-Bertos, J. Ramos-Torrecillas, O. García-Martínez, A. Guildford, M. Santin, C. Ruiz, Therapeutic doses of nonsteroidal anti-inflammatory drugs inhibit osteosarcoma MG-63 osteoblast-like cells maturation, viability, and biomineralization potential. Sci. World J. 2013, 809891 (2013). https://doi.org/10.1155/2013/809891CrossRef E. De Luna-Bertos, J. Ramos-Torrecillas, O. García-Martínez, A. Guildford, M. Santin, C. Ruiz, Therapeutic doses of nonsteroidal anti-inflammatory drugs inhibit osteosarcoma MG-63 osteoblast-like cells maturation, viability, and biomineralization potential. Sci. World J. 2013, 809891 (2013). https://​doi.​org/​10.​1155/​2013/​809891CrossRef
50.
Zurück zum Zitat Z. Naor, K.J. Catt, Mechanism of action of gonadotropin-releasing hormone. Involvement of phospholipid turnover in luteinizing hormone release. J. Biol. Chem. 256(5), 2226–2229 (1981)CrossRefPubMed Z. Naor, K.J. Catt, Mechanism of action of gonadotropin-releasing hormone. Involvement of phospholipid turnover in luteinizing hormone release. J. Biol. Chem. 256(5), 2226–2229 (1981)CrossRefPubMed
52.
Zurück zum Zitat Z. Naor, H.N. Jabbour, M. Naidich, A.J. Pawson, K. Morgan, S. Battersby, M.R. Millar, P. Brown, R.P. Millar, Reciprocal cross talk between gonadotropin-releasing hormone (GnRH) and prostaglandin receptors regulates GnRH receptor expression and differential gonadotropin secretion. Mol. Endocrinol. 21(2), 524–537 (2007). https://doi.org/10.1210/me.2006-0253CrossRefPubMed Z. Naor, H.N. Jabbour, M. Naidich, A.J. Pawson, K. Morgan, S. Battersby, M.R. Millar, P. Brown, R.P. Millar, Reciprocal cross talk between gonadotropin-releasing hormone (GnRH) and prostaglandin receptors regulates GnRH receptor expression and differential gonadotropin secretion. Mol. Endocrinol. 21(2), 524–537 (2007). https://​doi.​org/​10.​1210/​me.​2006-0253CrossRefPubMed
Metadaten
Titel
Neuroendocrine modulation by metamizole and indomethacin: investigating the impact on neuronal markers and GnRH release
verfasst von
Erkan Maytalman
Dilara Nemutlu Samur
Publikationsdatum
16.04.2024
Verlag
Springer US
Erschienen in
Endocrine
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-024-03822-3

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