Metastin
Kisspeptin is a protein present in the hypothalamus (a part of the brain that controls the release of several important hormones in the body). Kisspeptin plays a major role in the control of reproductive hormones in both men and women. Specifically, kisspeptin regulates the release of ‘gonadotrophin releasing hormone’ (GnRH) from the hypothalamus. GnRH, in turn, stimulates the release of the hormones, luteinising hormone (LH) and follicle stimulating hormone (FSH) from the pituitary gland, into the blood stream. These two hormones act on the testes in men and ovaries in women to produce sex-steroids, namely testosterone in men and oestradiol in women. Testosterone and oestradiol are the hormones responsible for the physical and emotional changes that occur during puberty in order to transition into adulthood.
Kisspeptin has a non-hormonal role too and was originally named ‘metastin’ due its ability to prevent the spread of cancer (metastasis).
Kisspeptin is released from nerve cells in the hypothalamus, together with two other proteins, neurokinin B and dynorphin. Consequently, the nerve cells making Kisspeptin, Dynorphin and Neurokinin B are popularly referred to as ‘KNDy’ (pronounced ‘candy’). It is believed that these proteins act in concert to induce the release of GnRH in a pulsating manner, which is important for its ability to stimulate LH and FSH.
Rarely, excess activity of kisspeptin in the hypothalamus due to genetic differences in some people can cause early puberty, also known as precocious puberty. Some studies have suggested that blood levels of kisspeptin are increased in children with precocious puberty.
Thankfully, the lack of kisspeptin action in the hypothalamus due to abnormalities in the relevant genes responsible are rare. When present, a lack of kisspeptin action in the hypothalamus results in insufficient GnRH, and in turn LH and FSH, and eventually a lack of testosterone (men) or oestradiol (women), which is a condition called ‘hypogonadotrophic hypogonadism’. Children with hypogonadotrophic hypogonadism due to genetic causes (called ‘congenital hypogonadotrophic hypogonadism’) are unable to proceed through puberty naturally and need hormone treatments to be able to do so.
Kisspeptin’s action in the hypothalamus can also be reduced due to other reasons aside from genetic causes to result in decreased reproductive function. One such example in which kisspeptin’s action in the hypothalamus is reduced, is called ‘hypothalamic amenorrhoea’. Amenorrhoea means a lack of periods. ‘Hypothalamic amenorrhoea’ is a specific type of amenorrhoea that occurs due to factors that can reduce the normal function of the hypothalamus, such as stress or insufficient energy availability. Research has suggested that in light of kisspeptin’s ability to stimulate the hypothalamus to secrete GnRH, giving kisspeptin could be used to restore reproductive health in women with hypothalamic amenorrhoea.
Kisspeptin also plays a role in the normal control of ovulation (release of an egg from the follicle in the ovary during the menstrual cycle). Research studies have shown that an injection of kisspeptin can be used to prepare eggs for use during fertility treatment. These eggs can be artificially fertilised in the laboratory (in vitro fertilisation), and then be placed back inside the womb to hopefully result in pregnancy. Kisspeptin can do this job without causing a dangerous side-effect of current IVF treatment called ‘ovarian hyperstimulation syndrome’ (OHSS). Further studies are needed to determine how kisspeptin compares with other fertility treatments to help couples with infertility.
Aside from its role in the hypothalamus, kisspeptin is also made by the placenta during pregnancy. It is thought to play a role in regulating the manner in which the placenta is formed. Kisspeptin levels in the blood go up massively during healthy pregnancy. Pregnant women with lower levels of kisspeptin in the blood may be more susceptible to pregnancy complications such as miscarriage. Therefore, in future pending further research, kisspeptin may have a role as a blood test to predict pregnancy complications.
Last reviewed: May 2021
