Kisspeptin-10

Overview

Kisspeptin-10 is the active, ten-amino-acid tail fragment of kisspeptin — an endogenous signalling protein with a key role in switching on the reproductive hormone axis. It is also called metastin (45-54).

Kisspeptin sits at the top of the chain that drives the reproductive hormones: it activates the GnRH neurons in the hypothalamus, which in turn prompt the pituitary to release LH and FSH. This makes kisspeptin a natural 'switch' for the axis that regulates puberty and fertility.

At Peptalis, kisspeptin-10 is available strictly for research use only — in-vitro laboratory research, not for human or animal use.

Mechanism of action

Kisspeptin-10 activates the KISS1 receptor (GPR54) on GnRH neurons; these release GnRH, prompting the pituitary to secrete LH and FSH.

At the top of the reproductive axis

• Kisspeptin binds the KISS1 receptor (GPR54) on the GnRH neurons in the hypothalamus and prompts them to release GnRH.
• GnRH in turn drives the pituitary to release the gonadotropins LH and FSH, which regulate the gonads.

Human evidence

• In humans, administration of kisspeptin-10 increases LH and FSH release, with a difference between men and women (Jayasena 2011).
• In men with type 2 diabetes and mild hypogonadism, kisspeptin-10 raised serum testosterone and LH (George 2013).

Research findings

• Mechanism/review: the kisspeptin-GnRH pathway in human reproductive health (Skorupskaite 2014)
• Human: kisspeptin-10 raises LH/FSH with sexual dimorphism in humans (Jayasena 2011)
• Human: in men with T2D and mild hypogonadism, testosterone and LH rise (George 2013)
• Human: kisspeptin-10 as a probe of the GnRH axis in healthy men (Skorupskaite 2017)

Mechanism

• The kisspeptin-GnRH pathway is well worked out in humans: kisspeptin activates GnRH neurons and thereby gonadotropin release (Skorupskaite 2014).

Human studies

• In healthy people, kisspeptin-10 increased LH and FSH release, with a clear difference between men and women (Jayasena 2011).
• In men with type 2 diabetes and mild biochemical hypogonadism, kisspeptin-10 stimulated serum testosterone and LH (George 2013).
• Kisspeptin-10 has also been used as a pharmacological probe to study the GnRH axis in healthy men (Skorupskaite 2017).

Research context

This profile describes what has been done and found in research. Regulatory and clinical facts are facts about the respective trials and authorities, not claims about a Peptalis product; the compound is for in-vitro laboratory research only (RUO).

Open questions

• Kisspeptin-10 has a short duration of action; most human studies are physiological/hormonal in nature.
• There is no approved indication; clinical applications (including fertility) are still being investigated.
• Longer-acting analogues and optimal dosing schedules are an active area of research.

Research outlook

Kisspeptin-10 is a well-characterized probe for the top of the reproductive axis (KISS1R-GnRH).

For laboratories studying the neuroendocrine regulation of reproduction, it is a clear, physiologically grounded model system.

Scientific interest

Opens a new axis in the neuro domain: the neuroendocrine control of reproduction.

Powerful, physiologically grounded mechanism (KISS1R → GnRH → LH/FSH).

Robust human evidence for the hormonal response.

Specifications

References

1. The effects of kisspeptin-10 on reproductive hormone release show sexual dimorphism in humans · Jayasena CN, et al. · J Clin Endocrinol Metab · 2011
2. Kisspeptin-10 stimulates serum testosterone and LH secretion in men with type 2 diabetes and mild biochemical hypogonadism · George JT, et al. · Clin Endocrinol (Oxf) · 2013
3. The kisspeptin-GnRH pathway in human reproductive health and disease · Skorupskaite K, et al. · Hum Reprod Update · 2014
4. Neurokinin 3 receptor antagonism decreases gonadotropin and testosterone secretion in healthy men · Skorupskaite K, et al. · Clin Endocrinol (Oxf) · 2017

Availability

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