Skip to main content

Advertisement

SpringerLink
Log in

Beneficial effects of irisin in experimental paroxetine-induced hyperprolactinemia

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Objective

It is known that selective serotonin reuptake inhibitors (SSRIs), represent an important and effective treatment of depression and other psychological disorders, these medications can increase prolactin levels mainly through activation of the serotonergic pathway. In this study, we aimed to determine the beneficial effects of irisin on paroxetine, a SSRI, induced hyperprolectinemia and in some other reproductive hormonal changes associated with hyperprolactinemia.

Methods

Thirty two male Spraque-Dawley rats were used and divided into four groups including sham-operated control (vehicle), irisin (100 ng/kg/day for 28 days with mini-osmotic pumps), paroxetine (treated with 20 mg/kg paroxetine by oral gavage), irisin and paroxetine+irisin groups (n = 8). Serum prolactin (PRL), kisspeptin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and 5-alpha reductase levels were determined with enzyme-linked immunosorbent analysis (ELISA).

Results

In animals treated with paroxetine, PRL level increased and testosterone level decreased significantly (p < 0.05). Serum LH level was significantly increased in the group, but no significant changes were observed in the FSH, kisspeptin and 5-alpha reductase levels. Serum prolactin levels was significantly decreased in the group treated with irisin. While no significant difference was observed in kisspeptin, FSH and 5-alpha reductase levels, an increase in serum LH and testosterone levels with irisin administration (p < 0.05).

Conclusion

In conclusion, chronic irisin exposure may reverse paroxetine-induced hyperprolactinemia. These results indicate that irisin may have the potential to be used as a therapeutic agent by primarily affecting paroxetine-induced increased prolactin and decreased testosterone levels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. R.P. Thom, J.L. Alexander, D. Baron, A. Garakani, L. Gross, J.H. Pine, R. Radhakrishnan, A. Slaby, C.R. Sumner, Selective serotonin reuptake inhibitors: How long is long enough? J. Psychiatr. Pract. 27(5), 361–371 (2021)

    Article  Google Scholar 

  2. S. Madhusoodanan, S. Parida, C. Jimenez, Hyperprolactinemia associated with psychotropics–a review. Hum. Psychopharmacol. 25(4), 281–297 (2010)

    Article  CAS  Google Scholar 

  3. M.R. Safarinejad, Evaluation of endocrine profile and hypothalamic-pituitary-testis axis in selective serotonin reuptake inhibitor-induced male sexual dysfunction. J. Clin. Psychopharmacol. 28(4), 418–423 (2008)

    Article  CAS  Google Scholar 

  4. D. La Torre, A. Falorni, Pharmacological causes of hyperprolactinemia. Therapeutics Clin. Risk Manag. 3(5), 929 (2007)

    Google Scholar 

  5. V. Bernard, J. Young, P. Chanson, N. Binart, New insights in prolactin: Pathological implications. Nat. Rev. Endocrinol. 11(5), 265–275 (2015)

    Article  CAS  Google Scholar 

  6. B.J. Kinon, J.A. Gilmore, H. Liu, U.M. Halbreich, Hyperprolactinemia in response to antipsychotic drugs: Characterization across comparative clinical trials. Psychoneuroendocrinology 28, 69–82 (2003)

    Article  CAS  Google Scholar 

  7. S. Bhattacharjee, R. Biswas, N. Mandal, Selective serotonin reuptake inhibitor-induced galactorrhea with hyperprolactinemia. Indian J. Psychiatry 63(6), 613–616 (2021)

    Article  Google Scholar 

  8. T.A. Lorenz, C.M. Meston, Exercise improves sexual function in women taking antidepressants: results from a randomized crossover trial. Depression Anxiety 31(3), 188–195 (2014)

    Article  Google Scholar 

  9. P. Boström, J. Wu, M.P. Jedrychowski, A. Korde, L. Ye, J.C. Lo, K.A. Rasbach, E.A. Boström, J.H. Choi, J.Z. Long et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481(7382), 463–468 (2012)

    Article  Google Scholar 

  10. J.Y. Huh, G. Panagiotou, V. Mougios, M. Brinkoetter, M.T. Vamvini, B.E. Schneider, C.S. Mantzoros, FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise. Metab.: Clin. Exp. 61(12), 1725–1738 (2012)

    Article  CAS  Google Scholar 

  11. S. Aydin, T. Kuloglu, S. Aydin, M. Kalayci, M. Yilmaz, T. Cakmak, S. Albayrak, S. Gungor, N. Colakoglu, I.H. Ozercan, A comprehensive immunohistochemical examination of the distribution of the fat-burning protein irisin in biological tissues. Peptides 61, 130–136 (2014)

    Article  CAS  Google Scholar 

  12. F. Gür, S. Timurkaan, M. Yalcin, A. Girgin, B. Gençer, Tarakçı, Immunohistochemical localization of irisin in mole rats (Spalax leucodon). Biotech. Histochemistry 92(4), 245–251 (2017)

    Google Scholar 

  13. Q. Jiang, Q. Zhang, A. Lian, Y. Xu, Irisin stimulates gonadotropins gene expression in tilapia (Oreochromis niloticus) pituitary cells. Anim. Reprod. Sci. 185, 140–147 (2017)

    Article  CAS  Google Scholar 

  14. Y. Luo, X. Qiao, Y. Ma, H. Deng, C.C. Xu, L. Xu, Irisin deletion induces a decrease in growth and fertility in mice. Reprod. Biol. Endocrinol.: RBE 19(1), 22 (2021)

    Article  CAS  Google Scholar 

  15. Ş. Kumsar, Ö. Ciğerli, E. Hasırcı, A.F. Akay, L. Peşkircioğlu, The relationship between serum irisin levels and erectile dysfunction in diabetic men (irisin and erectile dysfunction in diabetic patients). Andrologia 53(2), e13959 (2021)

    Article  CAS  Google Scholar 

  16. F. NANEES, H.I. REHAM, Role of irisin administration in modulating testicular function in adult obese albino rats. Med. J. Cairo Univ. 86(December), 4647–4655 (2018)

    Article  Google Scholar 

  17. A. Saleh, A. Hamed, A. Elfallah, E. Amin, Assessment of insulin resistance and serum levels of irisin in patients with idiopathic infertility. Benha J. Appl. Sci. 3(1), 145–146 (2018)

    Article  Google Scholar 

  18. T.R. de Jong, T. Pattij, J.G. Veening, M.D. Waldinger, A.R. Cools, B. Olivier, Effects of chronic selective serotonin reuptake inhibitors on 8-OH-DPAT-induced facilitation of ejaculation in rats: comparison of fluvoxamine and paroxetine. Psychopharmacology 179, 509–515 (2005)

    Article  Google Scholar 

  19. N. Ulker, A. Yardimci, N. Kaya Tektemur, O. Bulmus, S. Ozer Kaya, F. Gulcu Bulmus, G. Turk, M. Ozcan, S. Canpolat, Irisin may have a role in pubertal development and regulation of reproductive function in rats. Reprod. (Camb., Engl.) 160(2), 281–292 (2020)

    Article  CAS  Google Scholar 

  20. T. Reinehr, C. Elfers, N. Lass, C.L. Roth, Irisin and its relation to insulin resistance and puberty in obese children: a longitudinal analysis. J. Clin. Endocrinol. Metab. 100(5), 2123–2130 (2015)

    Article  CAS  Google Scholar 

  21. M. Hernandez-Trejo, G. Garcia-Rivas, A. Torres-Quintanilla, E. Laresgoiti-Servitje, Relationship between Irisin concentration and serum cytokines in mother and newborn. PloS one 11(11), e0165229 (2016)

    Article  Google Scholar 

  22. S. Tekin, A. Beytur, Y. Erden, A. Beytur, Y. Cigremis, N. Vardi, Y. Turkoz, I. Tekedereli, S. Sandal, Effects of intracerebroventricular administration of irisin on the hypothalamus-pituitary-gonadal axis in male rats. J. Cell. Physiol. 234(6), 8815–8824 (2019)

    Article  CAS  Google Scholar 

  23. E. Bastu, U. Zeybek, E.G. Gurevin, B.Y. Ozgor, F. Celik, N. Okumus, I. Demiral, O. Dural, C. Celik, H. Bulut, Effects of irisin and exercise on metabolic parameters and reproductive hormone levels in high-fat diet-induced obese female mice. Reprod. Sci. 25(2), 281–291 (2018)

    Article  CAS  Google Scholar 

  24. Y. Assyov, A. Gateva, V. Karamfilova, T. Gatev, I. Nedeva, T. Velikova, Z.A. Kamenov, Impact of testosterone treatment on circulating irisin in men with late-onset hypogonadism and metabolic syndrome. Aging Male 23(5), 1381–1387 (2020)

    Article  Google Scholar 

  25. Z. Kamenov, Y. Assyov, P. Angelova, A. Gateva, A. Tsakova, Irisin and testosterone in men with metabolic syndrome. Horm. Metab. Res. 49(10), 755–759 (2017)

    Article  CAS  Google Scholar 

  26. I.P. Doulamis, A. Tzani, P. Konstantopoulos, A. Daskalopoulou, T. Spinos, E. Bletsa, D. Mitsopoulou, M. Spinou, M.E. Brinia, K. Palaiopanos, Experimental hypogonadism: insulin resistance, biochemical changes and effect of testosterone substitution. J. Basic Clin. Physiol. Pharmacol. 30(3), (2019)

  27. A.B. Csoka, A. Bahrick, O.P. Mehtonen, Persistent sexual dysfunction after discontinuation of selective serotonin reuptake inhibitors. J. Sex. Med. 5, 227–233 (2008)

    Article  CAS  Google Scholar 

  28. F. Erdemir, D. Atilgan, F. Firat, F. Markoc, B.S. Parlaktas, E. Sogut, The effect of sertraline, paroxetine, fluoxetine and escitalopram on testicular tissue and oxidative stress parameters in rats. Int. Braz. J. Urol: Off. J. Braz. Soc. Urol. 40(1), 100–108 (2014)

    Article  Google Scholar 

  29. H.N. Bataineh, T. Daradka, Effects of long-term use of fluoxetine on fertility parameters in adult male rats. Neuro Endocrinol. Lett. 28(3), 321–325 (2007)

    CAS  PubMed  Google Scholar 

  30. C. Tanrikut, A.S. Feldman, M. Altemus, D.A. Paduch, P.N. Schlegel, Adverse effect of paroxetine on sperm. Fertil. Steril. 94(3), 1021–1026 (2010)

    Article  CAS  Google Scholar 

  31. O. Atli, M. Baysal, G. Aydogan-Kilic, V. Kilic, S. Ucarcan, B. Karaduman, S. Ilgin, Sertraline-induced reproductive toxicity in male rats: Evaluation of possible underlying mechanisms. Asian J. Androl. 19(6), 672 (2017)

    Article  CAS  Google Scholar 

  32. S. Bell, M. Shipman, A. Bystritsky, T. Haifley, Fluoxetine treatment and testosterone levels. Ann. Clin. Psychiatry.: Off. J. Am. Acad. Clin. Psychiatrists 18(1), 19–22 (2006).

    Article  Google Scholar 

  33. K. Wada, L. Hu, N. Mores, C.E. Navarro, H. Fuda, L.Z. Krsmanovic, K.J. Catt, Serotonin (5-HT) receptor subtypes mediate specific modes of 5-HT-induced signaling and regulation of neurosecretion in gonadotropin-releasing hormone neurons. Mol. Endocrinol. 20(1), 125–135 (2006)

    Article  CAS  Google Scholar 

  34. C. Sonigo, J. Bouilly, N. Carré, V. Tolle, A. Caraty, J. Tello, F.J. Simony-Conesa, R. Millar, J. Young, N. Binart, Hyperprolactinemia-induced ovarian acyclicity is reversed by kisspeptin administration. J. Clin. Investig. 122(10), 3791–3795 (2012)

    Article  CAS  Google Scholar 

  35. R.S. Brown, A.E. Herbison, D.R. Grattan, Prolactin regulation of kisspeptin neurones in the mouse brain and its role in the lactation-induced suppression of kisspeptin expression. J. Neuroendocrinol. 26(12), 898–908 (2014)

    Article  CAS  Google Scholar 

  36. R.P. Millar, C. Sonigo, R.A. Anderson, J. George, L. Maione, S. Brailly-Tabard, P. Chanson, N. Binart, J. Young, Hypothalamic-pituitary-ovarian axis reactivation by kisspeptin-10 in hyperprolactinemic women with chronic amenorrhea. J. Endocr. Soc. 1(11), 1362–1371 (2017)

    Article  Google Scholar 

  37. N. Ulker, A. Yardimci, E. Coban, M. Ozcan, S. Canpolat, Chronic irisin exposure decreases sexual incentive motivation in female rats. Physiol. Behav. 232, 113341 (2021)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Firat University, Faculty of Health Sciences, Department of Physiotherapy and Rehabilitation, Elazig, Turkey

    Zubeyde Ercan

  2. Firat University, Faculty of Medicine, Department of Physiology, Elazig, Turkey

    Meryem Sedef Dogru, Nazife Ulker Ertugrul, Ahmet Yardimci & Sinan Canpolat

Authors
  1. Zubeyde Ercan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Meryem Sedef Dogru
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nazife Ulker Ertugrul
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ahmet Yardimci
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sinan Canpolat
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S.C. and Z.E. contributed to the study’s conception and design. Material preparation and data collection and analysis were performed by N.U., A.Y., M.S.D. The first draft of the paper was written by Z.E and N.U. All authors commented on the previous versions of the paper. All authors read and approved the final paper.

Funding

This work was supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project No: 118S519).

Corresponding author

Correspondence to Zubeyde Ercan.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ercan, Z., Dogru, M.S., Ertugrul, N.U. et al. Beneficial effects of irisin in experimental paroxetine-induced hyperprolactinemia. Endocrine 76, 419–425 (2022). https://doi.org/10.1007/s12020-022-03010-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-022-03010-1

Keywords

Search

Navigation