Kisspeptin-10 (10mg)

Kisspeptin-10 Peptide

Kisspeptin-10 is a naturally occurring peptide protein that researcher suggest is encoded by the KISS1 gene.⁽²⁾ Kisspeptin is a product of the KISS1 gene, which is produced due to the cleavage of the original 145 amino acid peptide to a smaller peptide composed of 54 amino acids.⁽⁶⁾

KISS1 is a gene that is considered to suppress metastases of melanomas and breast carcinomas, thereby inhibiting abnormal cell growth and preventing cancer.⁽²⁾ Initially thought to be a metastasis suppressor, Kisspeptin-10 was later suggested to possess a different expression profile which may possibly allow it to function on the hypothalamus and pituitary gland, thereby possibly impacting the reproductive system.⁽³⁾

Several independent studies in the mid-2000s suggested that Kisspeptin-10 may play a role in hypogonadotropic hypogonadism as Kisspeptin-10 is considered to be a ligand of the G-protein coupled receptor 54 (GPR54).⁽⁵⁾ Research continues to date to explore this potential aspect of the Kisspeptin-10 peptide.

Hypogonadism is system disorder where reproductive organs produce less or no sex hormones. One of the forms of hypogonadism is called hypogonadotropic hypogonadism where the organism suffers from hypogonadism due to under-functioning of the pituitary gland or hypothalamus.⁽¹⁾ GnRH is considered to stimulate the pituitary gland to release follicle stimulating hormone (FSH) and luteinizing hormone (LH). Both FSH and LH are considered to regulate reproductive function.⁽¹⁾ Lack of these hormones, i.e. GnRH, FSH, and LH, are considered to be main factors of hypogonadotropic hypogonadism.

Kisspeptin-10 Overview

GPR54, also called KISS1 receptor (KISS1R)⁽⁷⁾, has been suggested by researchers to be an important GnRH receptor.⁽¹⁾ They further suggest that Kisspeptin-10 exhibits action by possibly binding to GPR54 receptors which may activate the reproductive axis by stimulating the release of GnRH and gonadotropin neurons.⁽⁷⁾

Kisspeptin-10 is a 54 amino acid peptide which is considered to be a product of the KISS1 gene. Researchers have isolated smaller peptide fragments such as Kisspeptin 10, 13, and 14, which all have been suggested to possess some biological activity towards GPR54.⁽⁷⁾ These smaller peptides have been posited to bind with a low affinity to the GPR54 receptors and possibly stimulate calcium mobilization, arachidonic acid release, and extracellular protein kinase phosphorylation.⁽⁷⁾ These events may depolarize the Kisspeptin-10 neurons, which might lead to the depolarization of the GnRH neurons, possibly modulating gonadotropin release to some extent.⁽⁹⁾

Research studies on Kisspeptin-10 have explored its potential in a wide variety of functions and impacts, and several hypotheses have been presented on the peptide's possible mechanisms of action:⁽⁸⁾

• May potentially stimulate GnRH release
• May potentially stimulate endogenous gonadotropin release in lesser fertile test models
• Peptide concentrations may possibly induce desensitization and suppression of the hypothalamus, pituitary gland, and gonadal axis

Research and Clinical Studies

Kisspeptin-10 and Reproduction

As part of this 2017 study,⁽¹⁰⁾ a literature review was conducted for all articles published during 1999 to 2016. Upon review of the articles, it was suggested that there is some experimental data to support the hypothesis the Kisspeptin-10 system (KISS1 gene and its products, GPR54 receptors) may possibly regulate the release of gonadotropin hormones.

Furthermore, there were reports stating that certain studies were conducted on experimental animal models representing similar characteristics as hypogonadotropic hypogonadism (HH) and polycystic ovarian syndrome (PCOS). These reports suggested that reproductive disorders such as HH and PCOS occur due to abnormalities in the KISS1 and GPR54 system. The outcome of this literature review suggested that Kisspeptin-10 may be a principal neuropeptide regulator of GnRH release.

Kisspeptin-10 and Delayed Hormonal Development

The main goal of this clinical study⁽¹³⁾ was to evaluate the potential of Kisspeptin-10 peptide in test subjects with stalled puberty. Researchers hypothesized that the peptide might stimulate the gonadal hormonal release and regulate the reproductive system in the subjects. 15 subjects were enrolled for this 2018 study where they were randomly introduced with either Kisspeptin-10 or gonadotropin releasing hormone (GnRH). The levels of luteinizing hormone (LH) were monitored overnight. All subjects were then presented with GnRH for 6 days and were again examined for the levels of LH. Of the 15 total subjects, 7 exhibited showed positive impacts as a possible result of Kisspeptin-10 presence, with increased levels of LH hormone.1 subject exhibited an intermediate response, and the other 7 exhibited no response as a result of peptide introduction.

Kisspeptin-10 and Emotional Modulation

The main purpose of this clinical study⁽¹⁴⁾ was to understand the potential of Kisspeptin-10 on limbic brain activity. Kisspeptin-10 was presented to 29 male test subjects, and the study results were monitored via neuroimaging and psychometric analysis. The data from the study suggested that the peptide led to some enhanced limbic brain activity. The subjects exhibited a reportedly increased response towards sexual and bonding stimuli.

Kisspeptin-10 and Reproductive Hormone Release

The key objective of this clinical study⁽¹⁵⁾ was to establish the potential of Kisspeptin-10 on reproductive hormone release. Kisspeptin-10 was presented to both male and female test subjects.  Results in the male subjects indicated that the levels of FSH and LH were increased following peptide presentation. In the female test subjects, no alterations were reported in the levels of LH and FSH during the menstrual cycle. However, during the preovulatory phase, the levels of FSH and LH were reportedly elevated.

Kisspeptin-10 and Food Intake

Kisspeptin-10 is considered to be widely distributed in brain sites including the hippocampus, cerebellum, posterior hypothalamus, and septum. Owing to its supposed vast distribution, and presence in the food intake regulating nuclei such as Arc found in the hypothalamus, this study⁽¹¹⁾ was conducted with the aim to examine the potential impact of Kisspeptin-10 on food intake. This experiment was conducted on adult male mice aged between 6 and 8 weeks, which were caged under normal temperatures and conditions. These mice were subjected to a standard rodent diet and tap water. Overnight fasted mice and the experimentally fed mice were presented with different concentrations of Kisspeptin-10 10 or placebo. Results suggested that the peptide in the overnight fasted mice may have led to a decrease in food intake during the first 3-to-12-hour period. The food intake then reportedly increased during the 12-to-16-hour period, which resulted in overall similar food intake compared to the placebo group. This result suggested that the peptide led to decrease in meal frequency and total meal time, and increased intervals between meals. However, meal size and eating rate was almost similar to that of the placebo mice.

Studies in Impaired Kisspeptin-10 Systems

As part of this study,⁽¹²⁾ the energetic and metabolic potential of Kisspeptin-10 was compared between healthy mice and mice with impaired Kisspeptin system. Results suggested that female mice with impaired Kisspeptin systems exhibited apparently dramatic increases in their body weight and significantly impaired glucose tolerance levels. While the peptide impaired female mice ate less than the healthy female mice, they were more obese, with reduced locomotor activity and respiratory rate. There was no reported difference found in the healthy male mice and male mice with impaired Kisspeptin systems. Both demonstrated normal body weight and glucose levels.

Kisspeptin-10 peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering.

References:

1. Hypogonadotropic hypogonadism. US National Library of Medicine. https://medlineplus.gov/ency/article/000390.htm
2. KISS1 KiSS-1 metastasis suppressor [Homo sapiens (humans)]. https://www.ncbi.nlm.nih.gov/gene/3814
3. Hussain, Mehboob A et al. “There is Kisspeptin - And Then There is Kisspeptin.” Trends in endocrinology and metabolism: TEM vol. 26,10 (2015): 564-572. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4587393/
4. Pasquier, J., Kamech, N., Lafont, A., Vaudry, H., Rousseau, K., & Dufour, S. (2014). MOLECULAR EVOLUTION OF GPCRS: Kisspeptin/kisspeptin receptors, Journal of Molecular Endocrinology, 52(3), T101-T117. https://jme.bioscientifica.com/view/journals/jme/52/3/T101.xml
5. Messager, S., Chatzidaki, E. E., Ma, D., Hendrick, A. G., Zahn, D., Dixon, J., Thresher, R. R., Malinge, I., Lomet, D., Carlton, M. B., Colledge, W. H., Caraty, A., & Aparicio, S. A. (2005). Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proceedings of the National Academy of Sciences of the United States of America, 102(5), 1761–1766. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC545088/
6. Mead, E. J., Maguire, J. J., Kuc, R. E., & Davenport, A. P. (2007). Kisspeptins: a multifunctional peptide system with a role in reproduction, cancer and the cardiovascular system. British journal of pharmacology, 151(8), 1143–1153. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2189831/
7. Rønnekleiv, O. K., & Kelly, M. J. (2013). Kisspeptin excitation of GnRH neurons. Advances in experimental medicine and biology, 784, 113–131. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019505/
8. Prague JK, Dhillo WS. Potential Clinical Use of Kisspeptin. Neuroendocrinology. 2015;102(3):238-45. doi: 10.1159/000439133. Epub 2015 Aug 7. https://pubmed.ncbi.nlm.nih.gov/26277870/
9. Tng E. L. (2015). Kisspeptin signalling and its roles in humans. Singapore medical journal, 56(12), 649–656. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678402/
10. Zeydabadi Nejad, S., Ramezani Tehrani, F., & Zadeh-Vakili, A. (2017). The Role of Kisspeptin in Female Reproduction. International journal of endocrinology and metabolism, 15(3), e44337. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702467/
11. Stengel, A., Wang, L., Goebel-Stengel, M., & Taché, Y. (2011). Centrally injected kisspeptin reduces food intake by increasing meal intervals in mice. Neuroreport, 22(5), 253–257. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063509/
12. Kristen P. Tolson et.al, Impaired kisspeptin signaling decreases metabolism and promotes glucose intolerance and obesity. The Journal of Clinical Investigation. Published June 17, 2014. https://www.jci.org/articles/view/71075
13. Chan, Y. M., Lippincott, M. F., Kusa, T. O., & Seminara, S. B. (2018). Divergent responses to kisspeptin in children with delayed puberty. JCI insight, 3(8), e99109. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931121/
14. Comninos, A. N., Wall, M. B., Demetriou, L., Shah, A. J., Clarke, S. A., Narayanaswamy, S., Nesbitt, A., Izzi-Engbeaya, C., Prague, J. K., Abbara, A., Ratnasabapathy, R., Salem, V., Nijher, G. M., Jayasena, C. N., Tanner, M., Bassett, P., Mehta, A., Rabiner, E. A., Hönigsperger, C., Silva, M. R., Dhillo, W. S. (2017). Kisspeptin modulates sexual and emotional brain processing in humans. The Journal of clinical investigation, 127(2), 709–719. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5272173/
15. Jayasena, C. N., Nijher, G. M., Comninos, A. N., Abbara, A., Januszewki, A., Vaal, M. L., Sriskandarajah, L., Murphy, K. G., Farzad, Z., Ghatei, M. A., Bloom, S. R., & Dhillo, W. S. (2011). The effects of kisspeptin-10 on reproductive hormone release show sexual dimorphism in humans. The Journal of clinical endocrinology and metabolism, 96(12), E1963–E1972. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232613/
16. G. M. K. Nijher, O. B. Chaudhri, R. Ramachandran et al., “The effects of kisspeptin-54 on blood pressure in humans and plasma kisspeptin concentrations in hypertensive diseases of pregnancy,” The British Journal of Clinical Pharmacology, vol. 70, no. 5, pp. 674–681, 2010. https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.2010.03746.x
17. d'Anglemont de Tassigny X, Jayasena CN, Murphy KG, Dhillo WS, Colledge WH. Mechanistic insights into the more potent effect of KP-54 compared to KP-10 in vivo. PLoS One. 2017 May 2;12(5):e0176821. doi: 10.1371/journal.pone.0176821. Erratum in: PLoS One. 2018 Jan 25;13(1):e0192014. PMID: 28464043; PMCID: PMC5413024. https://pubmed.ncbi.nlm.nih.gov/28464043/