WHAT IS KISSPEPTIN?

Kisspeptin is produced in the hypothalamus, is an important hormone that starts the release of several other hormones. It stimulates the release of gonadotropin-releasing hormone (GnRH) which then causes lutenizing hormone (LH) and follicle stimulating hormone (FSH) to be released from the pituitary gland. These hormones have a direct role in the production of testosterone and estradiol.

It has a non-hormonal role too and was originally named metastin after its ability to prevent the spread of cancer (metastasis). Recent data has also described its action in the control of metabolism. Recent data suggests that kisspeptin may play a role in food intake, glucose homeostasis and mediating the effect of energy balance on reproductive function. Thus, kisspeptin may have a direct role in regulating energy balance and may also be a direct regulator of metabolism.

Improper kisspeptin function or low kisspeptin levels can cause problems. Specifically, inadequate function of this hormone can cause male and female infertility. In females it can prevent menstruation which leads to other hormones dysfunction and absence of ovulation. Sometimes, just one injection of kisspeptin can trigger ovulation, which can allow for artificial insemination and in vitro fertilization using the woman's eggs.

A study from 2017 showed a significant decrease in serum kisspeptin for men with a low sperm count as well as infertile men. The serum kisspeptin levels were significantly higher in fertile men as compared to infertile males. The study provides a link between the kisspeptin levels and male reproductive fertility status. It can be considered a contributory factor in the control of testosterone, FSH and LH levels in males.

Having high levels of kisspeptin is not related to any conditions or symptoms, although preliminary research indicates that high kisspeptin levels in childhood can lead to early puberty, but this has not yet been proven.

Mechanism of action

Kisspeptins would appear to act directly on the nerve endings of GnRH neurons to control GnRH release, pulsatility, or discharge. Other studies show that Kisspeptins increase GnRH secretion as well as the level of mRNA. Kisspeptin is released in conjunction with two other hormones: dynorphin and neurokinin B, also called the KNDy neurons. The KNDy neurons are a fundamental element in regulating gonadotropin-releasing hormone (GnRH) pulses. These two hormones are not understood well, but early research indicates they may have a role in causing the release of kisspeptin.

Conclusions:

Gonadotropin injections (LH and FSH) constitute the classical treatment for infertility in females. Kisspeptin injections, which stimulate secretion of endogenous gonadotropin-releasing hormone (GnRH) inducing increased secretion of LH and FSH from the pituitary gland, could be a new treatment for medically assisted reproduction in women and increasing fertility and natural production of testosterone in men. This more physiological stimulation of might reduce the risk of overstimulation of the ovaries often associated with excessive injections of LH and FSH. Kisspeptin has now been safely and successfully used in both men and women, it is possible that in the future the manipulation of kisspeptin signaling may be used in the treatment of reproductive disorders.

Research:

• Mills EG, Ertl N, Wall MB, Thurston L, Yang L, Suladze S, Hunjan T, Phylactou M, Patel B, Muzi B, Ettehad D, Bassett PA, Howard J, Rabiner EA, Bech P, Abbara A, Goldmeier D, Comninos AN, Dhillo WS. Effects of Kisspeptin on Sexual Brain Processing and Penile Tumescence in Men With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial. JAMA Netw Open. 2023 Feb 1;6(2):e2254313. doi: 10.1001/jamanetworkopen.2022.54313. PMID: 36735255; PMCID: PMC9898824.
• Thurston L, Hunjan T, Ertl N, Wall MB, Mills EG, Suladze S, Patel B, Alexander EC, Muzi B, Bassett PA, Rabiner EA, Bech P, Goldmeier D, Abbara A, Comninos AN, Dhillo WS. Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial. JAMA Netw Open. 2022 Oct 3;5(10):e2236131. doi: 10.1001/jamanetworkopen.2022.36131. PMID: 36287566; PMCID: PMC9606846.
• Joanne L. Calley, Waljit S. Dhillo, "Effects of the Hormone Kisspeptin on Reproductive Hormone Release in Humans", Advances in Biology, vol. 2014, Article ID 512650, 10 pages, 2014. https://doi.org/10.1155/2014/512650
• George JT, Veldhuis JD, Roseweir AK, Newton CL, Faccenda E, Millar RP, Anderson RA: Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men. J Clin Endocrinol Metab 2011;96:E1228-E1236
• Dhillo WS, Chaudhri OB, Patterson M, Thompson EL, Murphy KG, Badman MK, McGowan BM, Amber V, Patel S, Ghatei MA, Bloom SR: Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males. J Clin Endocrinol Metab 2005;90:6609-6615
• Evaluation of serum kisspeptin role in male infertility. Ashraf T Abd Elmouttaleb, Doaa M Abd-Elatif, Eman M Rabie, Nashwa M Gouda, Osama A Hashem: Evaluation of serum kisspeptin role in male infertility. Intn J of Multidisciplinary research and dev Vol. 4, Issue 11 (2017) PAGES: 116-121
• Reproduction. 2014 Feb 3;147(3):R53-63. doi: 10.1530/REP-13-0509. Print 2014 Mar. Kisspeptin and energy balance in reproduction. De Bond JA1, Smith JT