Display options
Cite
Salehi MS, Khazali H, Mahmoudi F, et al. The effects of supraphysiological levels of testosterone on neural networks upstream of gonadotropin-releasing hormone neurons. Iran J Basic Med Sci. 2019;22(9):1065-1072doi: 10.22038/ijbms.2019.36127.8605.
Salehi, M. S., Khazali, H., Mahmoudi, F., & Janahmadi, M. (2019). The effects of supraphysiological levels of testosterone on neural networks upstream of gonadotropin-releasing hormone neurons. Iranian journal of basic medical sciences, 22(9), 1065-1072. https://doi.org/10.22038/ijbms.2019.36127.8605
Salehi, Mohammad Saied, et al. "The effects of supraphysiological levels of testosterone on neural networks upstream of gonadotropin-releasing hormone neurons." Iranian journal of basic medical sciences vol. 22,9 (2019): 1065-1072. doi: https://doi.org/10.22038/ijbms.2019.36127.8605
Salehi MS, Khazali H, Mahmoudi F, Janahmadi M. The effects of supraphysiological levels of testosterone on neural networks upstream of gonadotropin-releasing hormone neurons. Iran J Basic Med Sci. 2019 Sep;22(9):1065-1072. doi: 10.22038/ijbms.2019.36127.8605. PMID: 31807251; PMCID: PMC6880527.
Copy Download .nbib Format: NLM
Share it on

Iran J Basic Med Sci. 2019 Sep;22(9):1065-1072. doi: 10.22038/ijbms.2019.36127.8605.

The effects of supraphysiological levels of testosterone on neural networks upstream of gonadotropin-releasing hormone neurons.

Iranian journal of basic medical sciences

Mohammad Saied Salehi, Homayoun Khazali, Fariba Mahmoudi, Mahyar Janahmadi

Affiliations

  1. Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
  2. Department of Animal Physiology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
  3. Faculty of Basic Sciences, University of Mohaghegh Ardabili, Ardabil, Iran.
  4. Neuroscience Research Center and Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

PMID: 31807251 PMCID: PMC6880527 DOI: 10.22038/ijbms.2019.36127.8605

Abstract

OBJECTIVES: Several pathological conditions are associated with hyper-production of testosterone; however, its impacts are not well understood. Hence, we evaluated the effects of supraphysiological levels of testosterone on gonadotropin-releasing hormone (GnRH) system in the hypothalamus of male rats. Also, we assessed the expression of two excitatory (kisspeptin and neurokinin-B) and two inhibitory (dynorphin and RFamide-related-peptide) neuropeptides upstream of GnRH neurons as possible routes to relay androgen information.

MATERIALS AND METHODS: Gonadectomized (GDX) male rats received single injection of 100, 250 or 500 mg/kg testosterone undecanoate and three weeks later, posterior (PH) and anterior (AH) hypothalamus was dissected for evaluation of target genes using quantitative RT-PCR.

RESULTS: We found that GnRH mRNA in the PH was high in GDX rats and 500 mg/kg testosterone reduced GnRH level expression. Finding revealed extremely high level of Kiss1 mRNA in the PH of GDX rats. However, in GDX rats treated with different levels of testosterone, Kiss1 expression was not significantly different than control. We also found that testosterone replacement increased the Kiss1 mRNA level in the AH. Moreover, neurokinin-B mRNA level in PH of GDX rats was similar to control. However, excess testosterone levels were effective in significantly inducing the down-regulation of neurokinin-B expression. The basal level of dynorphin mRNA was increased following testosterone treatments in the AH, where we found no significant difference in the level of RFamide-related-peptide mRNA between the experimental groups.

CONCLUSION: Excess levels of testosterone could act differently from its physiological concentration to regulate hypothalamic androgen sensitive neurons to control GnRH cell.

Keywords: GnRH; Kisspeptin; Neurokinin B; RFRP; Testosterone

Conflict of interest statement

The authors declare that they have no conflict of interest.

References

  1. Brain Res. 1988 Jun 7;451(1-2):255-60 - PubMed
  2. Am J Physiol Endocrinol Metab. 2011 Jan;300(1):E202-10 - PubMed
  3. J Neuroendocrinol. 2017 Feb;29(2): - PubMed
  4. Endocrinology. 2012 Apr;153(4):1827-40 - PubMed
  5. Endocrinology. 2005 Jul;146(7):2976-84 - PubMed
  6. Endocrinology. 1990 Aug;127(2):523-32 - PubMed
  7. J Neuroendocrinol. 2008 Dec;20(12):1376-81 - PubMed
  8. Neuroendocrinology. 2011;94(4):323-32 - PubMed
  9. Neuroendocrinology. 2014;99(1):7-17 - PubMed
  10. Endocrinology. 2012 Oct;153(10):4818-29 - PubMed
  11. Methods. 2001 Dec;25(4):402-8 - PubMed
  12. Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2410-5 - PubMed
  13. Endocrinology. 1990 Feb;126(2):1080-6 - PubMed
  14. J Neurosci. 2009 Sep 23;29(38):11859-66 - PubMed
  15. Biol Reprod. 2001 Mar;64(3):735-42 - PubMed
  16. J Neurosci. 2009 Jul 22;29(29):9390-5 - PubMed
  17. Endocrinology. 2005 Apr;146(4):1835-42 - PubMed
  18. Brain Res. 1993 Oct 8;624(1-2):309-11 - PubMed
  19. Nature. 1981 Dec 24;294(5843):757-9 - PubMed
  20. Endocrinology. 2012 Nov;153(11):5428-39 - PubMed
  21. Neuropeptides. 2006 Apr;40(2):115-23 - PubMed
  22. J Neurosci. 2012 Feb 15;32(7):2388-97 - PubMed
  23. Life Sci. 1982 May 31;30(22):1915-9 - PubMed
  24. Exp Clin Endocrinol Diabetes. 2003 Jun;111(4):203-8 - PubMed
  25. J Comp Neurol. 2005 Aug 29;489(3):372-86 - PubMed
  26. Exp Brain Res. 1987;67(1):113-8 - PubMed
  27. Neuroendocrinology. 2004;80(4):264-72 - PubMed
  28. J Neuroendocrinol. 2010 Jul;22(7):692-700 - PubMed
  29. J Neurosci. 2010 Feb 24;30(8):3124-32 - PubMed
  30. Endocrinology. 2008 Mar;149(3):902-12 - PubMed
  31. Br J Sports Med. 2010 Jan;44(1):26-31 - PubMed
  32. Peptides. 2009 Jan;30(1):26-33 - PubMed
  33. J Clin Endocrinol Metab. 2010 Apr;95(4):1533-43 - PubMed
  34. Brain Res Mol Brain Res. 1999 Mar 20;66(1-2):200-4 - PubMed
  35. Iran J Basic Med Sci. 2018 Dec;21(12):1210-1220 - PubMed
  36. Endocrinology. 2004 Jun;145(6):2959-67 - PubMed
  37. Endocrinology. 1991 Jan;128(1):459-66 - PubMed
  38. Endocrinology. 2011 Apr;152(4):1684-90 - PubMed
  39. J Endocrinol. 1986 May;109(2):291-6 - PubMed
  40. Neurosci Lett. 1994 Dec 5;182(2):193-6 - PubMed
  41. Int J Fertil Steril. 2015 Oct-Dec;9(3):268-76 - PubMed
  42. J Neuroendocrinol. 2007 Jun;19(6):432-8 - PubMed

Publication Types