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Kisspeptin

Potential Benefits of Kisspeptin

  • Increases testosterone levels [1-5]
  • Lowers the risk of heart disease [6-11]
  • Boosts immunity [12-14]
  • Helps lose weight [15-17]
  • Prevents wrinkles and other signs of skin aging [18]
  • Prevents cancer [19-26]
  • Boosts brain power [27-29]
  • Treats fertility disorders [30-35]

What is Kisspeptin?

Kisspeptin is a peptide (a short chain of amino acids) that is produced by the hypothalamus in the brain. It plays an important role in human reproduction, secretion of aldosterone (regulates water and salt balance), tumor suppression, and kidney function.

How Kisspeptin Works?

Kisspeptin works by binding to a G-protein-coupled receptor (GPCR). This in turn stimulates the release of gonadotropin-releasing hormone (GnRH), leading to the secretion of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sexual steroids. LH, FSH, and sex steroids act on the gonads to stimulate the production of reproductive cells such as egg cells and sperm cells. By affecting the circulating levels of the hormones LH and FSH, kisspeptin increases testosterone levels.

Research on Kisspeptin

Increases Testosterone Levels

Kisspeptin has been shown to boost the hormone testosterone, which plays an integral role in reproductive health, bone health, cognitive function, fat distribution, and other vital bodily functions. The testosterone-boosting properties of kisspeptin are backed by a number of studies:

  1. In male volunteers, the administration of an intravenous (IV) infusion of kisspeptin significantly increased blood levels of LH, FSH, and testosterone concentrations compared with saline infusion. [1-2]
  2. In male adult rats, the administration of kisspeptin-54 into discrete regions of the hypothalamus potently increased blood levels of LH and testosterone. [3-4]
  3. In men with type 2 diabetes and mild biochemical hypogonadism (low sex hormone), kisspeptin-10 administration increased LH pulse frequency and LH secretion which in turn increased blood levels of testosterone. [5]

Lowers the Risk of Heart Disease

Evidence suggests that kisspeptin has cardioprotective properties:

  1. A study showed that kisspeptin can prevent the development of heart muscle injury. [6]
  2. In hypertensive mice, kisspeptin was found to significantly boost blood flow to the heart. [7]
  3. In human subjects, kisspeptin treatment decreased the risk of heart injury related to decreased blood flow. [8]
  4. A study showed that kisspeptin can help prevent the formation of abnormal plaques within the arteries of the heart. [9]
  5. A study showed that kisspeptin deficiency can cause acute myocardial infarction (AMI). [10]
  6. A study reported that kisspeptin has the potential to prevent the narrowing of the heart arteries. [11]

Boosts Immunity

Kisspeptin also has immune-modulating properties:

  1. A study showed that kisspeptin produced antiviral effects. [12]
  2. In rats, kisspeptin-54 vaccine-treated subjects demonstrated immunity against the Orf virus. [13]
  3. A study reported that kisspeptin has a role in the integration of reproductive and immune functions during pregnancy. [14]

Helps Lose Weight

Studies found that kisspeptin has the potential to promote weight loss:

  1. A study in mammals showed that kisspeptin can help reduce weight by decreasing food intake. [15]
  2. In mice, kisspeptin treatment reduced diet-induced obesity. [16]
  3. A study showed that alteration of kisspeptin may contribute directly or indirectly to human obesity, diabetes, or metabolic dysfunction. [17]

Prevents Wrinkles and other Signs of Skin Aging

A study showed that kisspeptin can be useful in improving UV-induced skin aging by modulating the production of stress-related genes. [18] This suggests that the peptide can be used as a therapeutic option for sun-damaged skin.

Prevents Cancer

The anti-cancer properties of kisspeptin are backed by a convincing number of evidence:

  1. A study showed that kisspeptin could potentially be used as a treatment for urogenital cancers. [19]
  2. A study found that kisspeptin exerts its anti-tumor effects via inhibition of proliferation, migration, and cell invasion. [20]
  3. A study showed that kisspeptin inhibited the progression of colorectal cancer. [21]
  4. A study also showed that kisspeptin treatment inhibited endometrial cancer invasion. [22]
  5. In urothelial carcinoma, kisspeptin prevented the spread of cancer cells into different body parts. [23]
  6. A study showed that kisspeptin enhanced the sensitivity of cancer cells to chemotherapeutic drugs. [24]
  7. In mice, kisspeptin prevented the spread of cancer cells by affecting their signaling pathways. [25]
  8. In human prostate cancer cells, kisspeptin induced the death of malignant cells. [26]

Boosts Brain Power

Kisspeptin has also been shown to play a role in maintaining optimal brain function:

  1. A study showed that kisspeptin helps regulate emotional processing in the brain. [27]
  2. A study also found that kisspeptin enhances brain activity in response to olfactory and visual cues of attraction in men. [28]
  3. A study reported that kisspeptin may aid in sexual and emotional brain processing. [29]

Treats Fertility Disorders

Evidence found that kisspeptin can help boost fertility:

  1. A study reported that kisspeptin can help treat fertility problems by regulating the production of gonadotropin-releasing hormone (GnRH). [30]
  2. In mice, kisspeptin signaling is essential for the activation of ovulation. [31]
  3. In rabbits, kisspeptin increased the pregnancy rate by boosting the production of the hormone progesterone. [32]
  4. A study showed that kisspeptin can increase fertility rate by modulating the release of GnRH. [33]
  5. A study showed that kisspeptin maintains normal reproductive function by stimulating GnRH release. [34]
  6. In women, an increased pregnancy rate was found to be associated with the maturation of kisspeptin neurons. [35]

Associated Side Effects of Kisspeptin

Kisspeptin side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on kisspeptin. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of kisspeptin. Despite this, it was listed as a side effect associated with kisspeptin even though these associated side effects are very uncommon.

Side effects associated with kisspeptin may include the following:

  • Diarrhea
  • Excessive sweating
  • Headache
  • Hot flushes
  • Postural dizziness
  • Shortened menstrual cycle

Reference

  1. Dhillo, W. S., Chaudhri, O. B., Patterson, M., Thompson, E. L., Murphy, K. G., Badman, M. K., McGowan, B. M., Amber, V., Patel, S., Ghatei, M. A., & Bloom, S. R. (2005). Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. The Journal of clinical endocrinology and metabolism, 90(12), 6609–6615. https://doi.org/10.1210/jc.2005-1468.
  2. George, J. T., Veldhuis, J. D., Roseweir, A. K., Newton, C. L., Faccenda, E., Millar, R. P., & Anderson, R. A. (2011). Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men. The Journal of clinical endocrinology and metabolism, 96(8), E1228–E1236. https://doi.org/10.1210/jc.2011-0089.
  3. Patterson, M., Murphy, K. G., Thompson, E. L., Patel, S., Ghatei, M. A., & Bloom, S. R. (2006). Administration of kisspeptin-54 into discrete regions of the hypothalamus potently increases plasma luteinising hormone and testosterone in male adult rats. Journal of neuroendocrinology, 18(5), 349–354. https://doi.org/10.1111/j.1365-2826.2006.01420.x.
  4. Thompson, E. L., Patterson, M., Murphy, K. G., Smith, K. L., Dhillo, W. S., Todd, J. F., Ghatei, M. A., & Bloom, S. R. (2004). Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic-pituitary-gonadal axis. Journal of neuroendocrinology, 16(10), 850–858. https://doi.org/10.1111/j.1365-2826.2004.01240.x.
  5. George, J. T., Veldhuis, J. D., Tena-Sempere, M., Millar, R. P., & Anderson, R. A. (2013). Exploring the pathophysiology of hypogonadism in men with type 2 diabetes: kisspeptin-10 stimulates serum testosterone and LH secretion in men with type 2 diabetes and mild biochemical hypogonadism. Clinical endocrinology, 79(1), 100–104. https://doi.org/10.1111/cen.12103.
  6. Zhang Y, Hou Y, Wang X, et al. The effects of kisspeptin-10 on serum metabolism and myocardium in rats. PLoS One. 2017;12(7):e0179164. Published 2017 Jul 10. doi:10.1371/journal.pone.0179164.
  7. Sawyer I, Smillie SJ, Bodkin JV, Fernandes E, O’Byrne KT, Brain SD. The vasoactive potential of kisspeptin-10 in the peripheral vasculature. PLoS One. 2011;6(2):e14671. Published 2011 Feb 9. doi:10.1371/journal.pone.0014671.
  8. Maguire JJ, Kirby HR, Mead EJ, Kuc RE, d’Anglemont de Tassigny X, Colledge WH, et al. (2011) Inotropic Action of the Puberty Hormone Kisspeptin in Rat, Mouse and Human: Cardiovascular Distribution and Characteristics of the Kisspeptin Receptor. PLoS ONE 6(11): e27601. https://doi.org/10.1371/journal.pone.0027601.
  9. Available from https://www.ahajournals.org/doi/full/10.1161/JAHA.117.005790.
  10. Shojaei, M., Erfanian, S., Sotoodeh Jahromi, A., Yusefi, N., Madani, A., Khoshfetrat, M., & Hojjat-Farsangi, M. (2018). Kisspeptin serum levels in acute myocardial infarction patients and healthy individuals. Biomedical Research and Therapy, 5(3), 2111-2118. https://doi.org/10.15419/bmrat.v5i3.424.
  11. Emma J. Mead, Janet J. Maguire, Rhoda E. Kuc, Anthony P. Davenport, Kisspeptins Are Novel Potent Vasoconstrictors in Humans, with a Discrete Localization of Their Receptor, G Protein-Coupled Receptor 54, to Atherosclerosis-Prone Vessels, Endocrinology, Volume 148, Issue 1, 1 January 2007, Pages 140–147, https://doi.org/10.1210/en.2006-0818.
  12. Huang H, Xiong Q, Wang N, et al. Kisspeptin/GPR54 signaling restricts antiviral innate immune response through regulating calcineurin phosphatase activity. Sci Adv. 2018;4(8):eaas9784. Published 2018 Aug 8. doi:10.1126/sciadv.aas9784.
  13. Wassie, T., Fanmei, Z., Jiang, X. et al. Recombinant B2L and Kisspeptin-54 DNA Vaccine Induces Immunity Against Orf Virus and Inhibits Spermatogenesis In Rats. Sci Rep 9, 16262 (2019). https://doi.org/10.1038/s41598-019-52744-y.
  14. Gorbunova, O. L., & Shirshev, S. V. (2020). Role of Kisspeptin in Regulation of Reproductive and Immune Reactions. Biochemistry. Biokhimiia, 85(8), 839–853. https://doi.org/10.1134/S0006297920080015.
  15. Wolfe A, Hussain MA. The Emerging Role(s) for Kisspeptin in Metabolism in Mammals. Front Endocrinol (Lausanne). 2018;9:184. Published 2018 Apr 24. doi:10.3389/fendo.2018.00184.
  16. Janette H. Quennell, Christopher S. Howell, Juan Roa, Rachael A. Augustine, David R. Grattan, Greg M. Anderson, Leptin Deficiency and Diet-Induced Obesity Reduce Hypothalamic Kisspeptin Expression in Mice, Endocrinology, Volume 152, Issue 4, 1 April 2011, Pages 1541–1550, https://doi.org/10.1210/en.2010-1100.
  17. Available from https://www.jci.org/articles/view/71075.
  18. Lee, Kyung-Eun & Jeong, Sugyeong & Yun, Seok & Kyung, Seoyeon & Sophie, Abadie & Moh, Sang Hyun & Seo, Hyo & Park, Myeong & Kang, Seunghyun & Yeo, Hyeonju. (2020). Synthesis of Kisspeptin-Mimicking Fragments and Investigation of their Skin Anti-Aging Effects. International Journal of Molecular Sciences. 21. 8439. 10.3390/ijms21228439.
  19. Wahab, F., Atika, B., Shahab, M. et al. Kisspeptin signalling in the physiology and pathophysiology of the urogenital system. Nat Rev Urol 13, 21–32 (2016). https://doi.org/10.1038/nrurol.2015.277.
  20. Ciaramella V, Della Corte CM, Ciardiello F, Morgillo F. Kisspeptin and Cancer: Molecular Interaction, Biological Functions, and Future Perspectives. Front Endocrinol (Lausanne). 2018;9:115. Published 2018 Mar 27. doi:10.3389/fendo.2018.00115.
  21. Kim JN, Kim TH, Yoon JH, Cho SG. Kisspeptin Inhibits Colorectal Cancer Cell Invasiveness by Activating PKR and PP2A. Anticancer Res. 2018 Oct;38(10):5791-5798. doi: 10.21873/anticanres.12918. PMID: 30275201.
  22. Schmidt E, Haase M, Ziegler E, Emons G, GrĂĽndker C. Kisspeptin-10 inhibits stromal-derived factor 1-induced invasion of human endometrial cancer cells. Int J Gynecol Cancer. 2014 Feb;24(2):210-7. doi: 10.1097/IGC.0000000000000050. PMID: 24407584.
  23. Takeda T, Kikuchi E, Mikami S, Suzuki E, Matsumoto K, Miyajima A, Okada Y, Oya M. Prognostic role of KiSS-1 and possibility of therapeutic modality of metastin, the final peptide of the KiSS-1 gene, in urothelial carcinoma. Mol Cancer Ther. 2012 Apr;11(4):853-63. doi: 10.1158/1535-7163.MCT-11-0521. Epub 2012 Feb 24. PMID: 22367780.
  24. Wang H, Jones J, Turner T, et al. Clinical and biological significance of KISS1 expression in prostate cancer. Am J Pathol. 2012;180(3):1170-1178. doi:10.1016/j.ajpath.2011.11.020.
  25. Kim, T., & Kim, T. (2017). Kisspeptin inhibits cancer growth and metastasis via activation of EIF2AK2. Molecular Medicine Reports, 16, 7585-7590. https://doi.org/10.3892/mmr.2017.7578.
  26. Available from https://cancerres.aacrjournals.org/content/69/17/7062.
  27. Comninos AN, Wall MB, Demetriou L, et al. Kisspeptin modulates sexual and emotional brain processing in humans. J Clin Invest. 2017;127(2):709-719. doi:10.1172/JCI89519.
  28. Yang L, Demetriou L, Wall MB, et al. Kisspeptin enhances brain responses to olfactory and visual cues of attraction in men. JCI Insight. 2020;5(3):e133633. Published 2020 Feb 13. doi:10.1172/jci.insight.133633.
  29. Available from https://www.karger.com/Article/Fulltext/481137#.
  30. Clarke H, Dhillo WS, Jayasena CN. Comprehensive Review on Kisspeptin and Its Role in Reproductive Disorders. Endocrinol Metab (Seoul). 2015;30(2):124-141. doi:10.3803/EnM.2015.30.2.124.
  31. Available from https://www.jneurosci.org/content/28/35/8691.
  32. Maranesi, M., Petrucci, L., Leonardi, L. et al. Kisspeptin/kisspeptin receptor system in pseudopregnant rabbit corpora lutea: presence and function. Sci Rep 9, 5044 (2019). https://doi.org/10.1038/s41598-019-41623-1.
  33. León, S., Barroso, A., Vázquez, M. et al. Direct Actions of Kisspeptins on GnRH Neurons Permit Attainment of Fertility but are Insufficient to Fully Preserve Gonadotropic Axis Activity. Sci Rep 6, 19206 (2016). https://doi.org/10.1038/srep19206.
  34. Available from https://journals.physiology.org/doi/full/10.1152/physiol.00009.2010.
  35. Tng EL. Kisspeptin signalling and its roles in humans. Singapore Med J. 2015;56(12):649-656. doi:10.11622/smedj.2015183.
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