Kisspeptin: The Complete Guide

Research suggests the KISS1 gene codes for a peptide-protein called Kisspeptin [ii]. If you want to know more about this peptide, read the complete guide.

The 145-amino-acid precursor peptide is cleaved into two 54-amino-acid peptides [v], one of which is Kisspeptin, a product of the KISS1 gene. Studies suggest KISS1 is a gene that may mitigate cancer by suppressing the spread of malignant cells, namely melanomas and breast carcinomas [ii].

Researchers speculate Kisspeptin was first identified as a potential metastasis suppressor; nevertheless, its unique expression profile suggested another potential to act on the hypothalamus and pituitary gland, which may affect reproduction [iii].

Kisspeptin Peptide History

In the middle of the 1990s, chromosome 6 was introduced into a cancer cell. It was suggested that this chromosome (later termed the KISS1 gene) may have mitigated the formation of metastasis and the spread of cancerous cells.

After another decade, a breakthrough study posited how the Kisspeptin peptide works.

Kisspeptin is considered a ligand of the G-protein coupled receptor 54 (GPR54), and considerable research published around the middle of the millennium speculated that it may play a significant role in hypogonadotropic hypogonadism. To this day, scientists are still digging into this facet of the Kisspeptin peptide.

Kisspeptin and Reproduction

Hypogonadism refers to a condition of the reproductive system in which the testes of male and female ovaries produce inadequate or no sex hormones. Subjects with hypogonadism caused by hypopituitarism or hypothalamic dysfunction are said to have hypogonadotropic hypogonadism [i].

Scientists consider that normal hormone production starts with the release of gonadotropin-releasing hormones (GnRH) from the hypothalamus. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) appears to be secreted by the pituitary gland in response to GnRH, and, when combined, FSH and LH may stimulate the ovaries and testes, resulting in healthy quantities of estrogen in females and sperm in males [i].

Inadequate GnRH, FSH, and LH production is considered to be the leading cause of hypogonadotropic hypogonadism, and may have serious impact on sexual maturation.

What role does Kisspeptin play?

Research suggests the GnRH receptor GPR54, also known as the KISS1 receptor (KISS1R) [vi], may be critical for the onset of sexual maturation in animals [iv].

Scientists hypothesize that by binding to GPR54 receptors, Kisspeptin may stimulate the release of GnRH and gonadotropin neurons, activating the reproductive axis. Studies suggest more than 85% of GnRH neurons may be stimulated by centrally given Kisspeptin, leading to increased FSH and LH secretion in the body.

Kisspeptin, the product of the KISS1 gene, is a peptide of 54 amino acids. Smaller peptide fragments with biological activity towards GPR54 [vi] include Kisspeptins 10, 13, and 14. Research speculates these shorter peptides may activate calcium mobilization, arachidonic acid release, and extracellular protein kinase phosphorylation [vi] by binding with a low affinity to the GPR54 receptors. These processes cause depolarization of the Kisspeptin neurons, depolarizing the GnRH neurons and controlling the release of gonadotropins [vii].

As studies suggest, Kisspeptin may promote the release of GnRH by directly stimulating the GnRH neurons rather than the pituitary gland, where GPR54 is also expressed.Researchers hypothesize that Kisspeptin may excite most of the GnRH neurons.

Kisspeptin- Female Reproduction

This 2017 research [viii] included a comprehensive literature search of all relevant studies published between 1999 and 2016.

Based on the literature, it was speculated that the Kisspeptin system (KISS1 gene and its products, GPR54 receptors) might be critical for initiating sexual maturation and regulating gonadotropin hormone secretion.

Additionally, it has been reported that some research has been done using experimental animal models with features similar to those of hypogonadotropic hypogonadism (HH) and polycystic ovary syndrome (PCOS). These studies speculated that defects in the KISS1 and GPR54 systems might contribute to developing reproductive diseases, including HH and PCOS.

Kisspeptin- Fertility

The primary purpose of this research [ix] was to determine if Kisspeptin impacted the secretion of reproductive hormones in otherwise healthy males and females.

Kisspeptin was given to males and females, respectively. Male subjects seemed to have increased FSH and LH levels after getting either quantity of the peptide.

The study suggested LH and FSH levels in female subjects did not change during the follicular phase of the menstrual cycle (days 2–10). However, both FSH and LH levels appeared significantly higher in females during the preovulatory phase (the 15-16 days before the beginning of the next menstrual cycle).

These findings speculated that Kisspeptin might increase FSH and LH levels in both sexes throughout the ovulation preparation period. 

Only academic and scientific institutions are allowed to use Kisspeptin. If you are a licensed professional interested in finding Kisspeptin-10 for sale for your clinical studies, you can visit Biotech Peptides. Please note that none of the items listed are approved for human or animal consumption. Laboratory research chemicals are only for in-vitro and in-lab use. Any kind of physical introduction is illegal. Only authorized academics and working professionals may make purchases. The content of this article is intended only for instructional purposes.

References

[i] Hypogonadotropic hypogonadism. US National Library of Medicine. https://medlineplus.gov/ency/article/000390.htm

[ii] KISS1 KiSS-1 metastasis suppressor [Homo sapiens (humans)]. https://www.ncbi.nlm.nih.gov/gene/3814

[iii] 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/

[iv] 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/

[v] 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/

[vi] 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/

[vii] 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/

[viii] 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/

[ix] 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/


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