Kisspeptin-10

Kisspeptin-10, a low molecular weight peptide fragment of the kisspeptin protein family, is the key player in human endocrinology, particularly in regulating reproductive health. Discovered for its role in the hypothalamic-pituitary-gonadal (HPG) axis, Kisspeptin-10 gained considerable attention for its possible applications in fertility treatments, hormonal therapies, and many neurological studies. Naturally occurring in humans, this peptide interacts with the G-protein-coupled receptor GPR54, which initiates a series of biological reactions crucial for pubertal development and reproductive health.

Kisspeptin – 10 Research

Increasing Testosterone

Based on the studies conducted on animal models, Kisspeptin can affect circulating levels of FSH and LH, altering testosterone levels. However, this alteration seems to be sex specific. In male rats, Kisspeptin increases testosterone levels, while in female rats, it doesn't have a visible effect on testosterone. In one trial, male rats were administered a derivative of Kisspeptin, and they showed a major increase in plasma testosterone levels, nearly three-fold, after just 90 minutes.

A different analog of Kisspeptin has been found to change the pulse frequency of LH in male rats, indicating that this peptide can help fine-tune the normal pulsatile release of sex hormones.

A study involving another batch of healthy mice, which were given Kisspeptin – 10, revealed a dose-dependent and rapid boost in serum LH levels and concomitant rise in testosterone levels. These findings are important because, in the future, this peptide could be used in a variety of settings, from testosterone levels to pregnancy and more.

Energy Balance

Kisspeptin neurons are known to be sensitive to the energy status of an individual. Both severe over-nutrition and under-nutrition can dull the action of Kisspeptin neurons in boosting GnRH release. In laboratory settings, these drastic changes in energy balance can cause infertility in both female and male rats. However, this process seems to be mediated by Kisspeptin.

Therefore, it's well understood that Kisspeptin production and release are sensitive to energy balance. What is becoming evident is that this peptide may manage energy balance. These findings were based on the mice research in which the Kiss1r or Kisspeptin receptor was removed via genetic manipulation.

During this research, mice showed an increase in obesity and a reduction in energy expenditure. The Kisspeptin receptor seems to be located in brown adipose tissue and adipose fat tissue. Therefore, it shouldn't surprise us that Kisspeptin plays a significant role in energy balance, considering reproductive fitness and energy status have always been tightly connected.

Cancer Research

Twenty years ago, scientists discovered that Kisspeptin can suppress melanoma metastasis, a type of skin cancer, by as much as 95%. It seems that this peptide generates this effect by minimizing cancer cell migration.

There were also questions about whether this peptide can minimize cell adhesion and thereby prevent cancer cells from attaching themselves to other tissues and invading them. In laboratory settings, examining different types of cancer reveals that thyroid, skin, ovarian, pancreatic, prostate, GI, bladder, and breast cancers all show changes in Kisspeptin changes; generally, they decreased, confirming the claims that this peptide plays a role in the spread of cancer.

It's not that this peptide doesn't work, but its effects are diverse, and it's really challenging to determine its exact impact on various cancer cells. Dr. Floriana Morgillo pleads with researchers to explore the complexities of Kisspeptin and understand the massive potential of this peptide in cancer treatment.

Research conducted on mice suggests that this peptide effectively prevents metastasis across various organs, significantly reducing the disease burden and extending the lifespan of the subjects.

In 2020, an amazing connection was discovered between Kisspeptin, cancer, and melatonin when, in an experiment, scientists managed to connect levels of Kisspeptin with daylight exposure. In a study involving mice exposed to daylight and darkness, they found significantly different levels of Kisspeptin and low melatonin levels.

Memory Enhancement

It seems that certain analogs to Kisspeptin are crucial in the area of the brain responsible for orientation in 3-D space and memory consolidation. Research in rodents indicates that administration of these peptides can help reverse the navigational and learning impairment commonly observed in cases of ethanol intoxication.

This implies that Kisspeptin and its analogues are vital in information encoding, potentially making this peptide a valuable target for addressing learning impairments associated with specific chronic and genetic conditions.

Even though this research is in its early stages, it helps broaden our understanding of learning and helps us further develop nootropics that can stimulate damaged brains and health to boost their functioning.

Impact on Mood

Just like energy status and reproduction are interconnected, so are emotion and reproduction. Considering Kisspeptin's role in energy homeostasis and reproduction, scientists have investigated how this peptide might affect behavior and emotions.

To explore this connection, they compared Kisspeptin to a placebo. They administered Kisspeptin to mice, and those who were given this peptide showed enhanced limbic brain activity, like increased drive, reward-seeking behavior, and overall improved mood. These findings will help scientists understand mood, drive, and motivation.

Kidney and Heart

There has been a lot of discussion about the role of Kisspeptin in reproductive hormone control and reproduction. It might come as a surprise, but Kisspeptin is an important component when it comes to kidneys. This peptide and its receptors are present in various regions of the kidney, where they are thought to be involved in regulating kidney function.

A study based on mice revealed that lack of Kiss1 receptor affected glomerular development. However, the exact role of Kisspeptin in the kidney is not understood, but it might relate to cardiovascular development and vascular response to injury.

Another study of mice dealing with cardiovascular diseases indicates that Kisspeptin might have an important role in certain vascular beds and not others. It might control vasoconstriction and even cardiac output in particular settings.

Summary 

While Kisspeptin shows a lot of promise in laboratory settings and impacts a wide range of conditions, we still need additional research before applying this peptide to humans. 

 References:

1. W. S. Dhillo et al., “Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males,” J. Clin. Endocrinol. Metab., vol. 90, no. 12, pp. 6609–6615, Dec. 2005, doi: 10.1210/jc.2005-1468.
2. J. T. George et al., “Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men,” J. Clin. Endocrinol. Metab., vol. 96, no. 8, pp. E1228-1236, Aug. 2011, doi: 10.1210/jc.2011-0089.
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6. P. Pazarci et al., “The effects of daylight exposure on melatonin levels, Kiss1 expression, and melanoma formation in mice,” Croat. Med. J., vol. 61, no. 1, pp. 55–61, Feb. 2020.
7. E. Gibula-Tarlowska and J. H. Kotlinska, “Kissorphin improves spatial memory and cognitive flexibility impairment induced by ethanol treatment in the Barnes maze task in rats,” Behav. Pharmacol., vol. 31, no. 2 & 3, pp. 272–282, Apr. 2020, doi: 10.1097/FBP.0000000000000557.
8. A. N. Comninos et al., “Kisspeptin modulates sexual and emotional brain processing in humans,” J. Clin. Invest., vol. 127, no. 2, pp. 709–719, doi: 10.1172/JCI89519.
9. M. Bhattacharya and A. V. Babwah, “Kisspeptin: Beyond the Brain,” Endocrinology, vol. 156, no. 4, pp. 1218–1227, Apr. 2015, doi: 10.1210/en.2014-1915.
10. Ciaramella V, Della Corte CM, Di Mauro C, Tomassi S, Di Maro S, Troiani T, Martinelli E, Bianco R, Cosconati S, Pierantoni R, Meccariello R, Chianese R, Ciardiello F, Morgillo F. Antitumor efficacy of Kisspeptin in human malignant mesothelioma cells. Oncotarget. 2018 Apr 10;9(27):19273-19282. doi: 10.18632/oncotarget.25018. PMID: 29721201; PMCID: PMC5922395.