Kisspeptin
| KiSS-1 metastasis suppressor | ||
|---|---|---|
| Properties of human protein | ||
| Identifier | ||
| Gene names | KISS1 ; KiSS-1; MGC39258 | |
| External IDs | ||
| Drug information | ||
| Drug class | hormone | |
| Occurrence | ||
| Parent taxon | Eutheria (higher mammals) | |
| Orthologue | ||
| human | mouse | |
| Entrez | 3814 | 280287 |
| Ensemble | ENSG00000170498 | |
| UniProt | Q15726 | |
| Refseq (mRNA) | NM_002256 | NM_178260 |
| Refseq (protein) | NP_002247 | NP_839991 |
| Gene locus | Chr 1: 202.43 - 202.43 Mb | |
| PubMed search | 3814 |
280287
|
The peptide hormone kisspeptin is the product of the KiSS1 gene. As a ligand , it binds to the G-protein coupled KiSS1 receptor , also known as GPR54 . Originally, KiSS1 was identified as a suppressor gene; in humans it is able to suppress the metastasis of skin cancer and breast cancer . The important role of kisspeptin KiSS1 receptor signaling for the onset of gonadoliberin release at the beginning of puberty has only recently been recognized and is still the subject of current research.
discovery
In 1999 the receptor for kisspeptin was found in rats and identified as a G protein-coupled receptor. It was not until 2001 that the matching ligand, the product of the KiSS1 gene, was discovered. Its function was first described for humans as that of a suppressor morning for metastases. Subsequent studies were able to show that loss-of-function mutations of the KiSS1 gene prevent puberty in humans by causing hypogonadotropic underfunction of the gonads ( hypogonadism ). From this it was concluded that at the beginning of puberty the kisspeptin-KiSS1-receptor signal transduction is necessary for the initiation of the release of gonadotropin ( LH / FSH ).
Kisspeptin is synthesized in the hypothalamus.
KiSS1 and Kisspeptin were named by their discoverers after a well-known chocolate product from the Hershey Company in Hershey (Pennsylvania) .
Kisspeptin neurons
In mice, kisspeptin is expressed (formed) in neurons of these nuclei of the hypothalamus :
- Nucleus arcuatus ( Arc )
- Nucleus periventricularis anteroventralis ( AVPV )
- Periventricular nucleus ( PE )
- Nucleus praeopticus anterodorsalis ( AP )
Kisspeptin neurons are found in cell bodies such as Arc and AVPV . They send offshoots into the praeoptica region of the hypothalamus , where gonadoliberin cell bodies are found in large numbers. These relationships suggest that kisspeptin fibers are closely anatomically related to gonadoliberin-forming (parvicellular) neurons. In fact, kisspeptin seems to act on gonadoliberin neurons via KiSS1R and thus stimulate gonadoliberin release.
The gonads also release steroids that regulate FSH and LH levels via gonadoliberin. Therefore, for effective regulation of gonadoliberin, kisspeptin must respond to the steroid hormones present in the blood. Thus at least two ways of regulation are conceivable:
- Kisspeptin neurons express steroid receptors (such as ERα, ERβ, and the androgen receptor )
- Kisspeptin neurons are regulated by the steroid hormone level in the blood through an intermediate mechanism
By expressing KiSS1 mRNA together with receptors for steroid hormones, it was possible to show that steroid sex hormones in mice of both sexes have a direct effect on KiSS1 neurons.
Kisspeptin and Puberty
The following experimental results suggest that kisspeptin is involved in puberty:
- Animals in which the KiSS1 receptor has lost its function as a result of spontaneous or directed mutations no longer enter puberty
- The activation of the gonadoliberin neurons is the triggering event for the onset of puberty
- Peripheral administration of Kisspeptin at 25 days of age, prepubertal rats stimulates the secretion of LH and induces ovulation ( ovulation )
- If kisspeptin is involved in puberty, KiSS1 and / or KiSS1R mRNA should be synthesized to a greater extent. RT-PCR assays and semi-quantitative studies support this hypothesis
- The electrophysiological response of the gonadoliberin neurons to kisspeptin appears to change dramatically during puberty
Type of effect
Apparently, kisspeptin activates the gonadoliberin cell bodies through direct action:
- the response of neurons to kisspeptin is not suppressed by tetrodotoxin , although it effectively blocks nerve conduction.
- In patch-clamp measurements on gramicidin- perforated cells from prepubertal mice, only 30% of the gonadoliberin neurons react to kisspeptin, compared with 60% in adult animals.
- Only adult mice respond to low levels of kisspeptin; From this it is concluded that the development of gonadoliberin neurons is activated by kisspeptin during puberty.
swell
- ↑ Messager S, Chatzidaki EE, Ma D, Hendrick AG, Zahn D, Dixon J, Thresher RR, Malinge I, Lomet D, Carlton MB, Colledge WH, Caraty A, Aparicio SA: Kisspeptin directly stimulates gonadotropin-releasing hormone release via G. protein-coupled receptor 54 . In: Proc. Natl. Acad. Sci. USA . 102, No. 5, 2005, pp. 1761-6. doi : 10.1073 / pnas.0409330102 . PMID 15665093 .
- Jump up ↑ Smith JT, Clifton DK, Steiner RA: Regulation of the neuroendocrine reproductive axis by kisspeptin-GPR54 signaling . In: Reproduction . 131, No. 4, 2006, pp. 623-30. doi : 10.1530 / rep.1.00368 . PMID 16595713 .
- ↑ Dungan HM, Clifton DK, Steiner RA: Minireview: kisspeptin neurons as central processors in the regulation of gonadotropin-releasing hormone secretion . In: Endocrinology . 147, No. 3, 2006, pp. 1154-8. doi : 10.1210 / en.2005-1282 . PMID 16373418 .
- Jump up ↑ Lee D, Nguyen T, O'Neill G, Cheng R, Liu Y, Howard A, Coulombe N, Tan C, Tang-Nguyen A, George S, O'Dowd B: Discovery of a receptor related to the galanin receptors . In: FEBS Lett . 446, No. 1, 1999, pp. 103-7. PMID 10100623 .
- ↑ Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderlösungen J, Le Poul E, Brézillon S, Tyldesley R, Suarez-Huerta N, Vandeput F, Blanpain C, Schiffmann S, Vassart G, Parmentier M: The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54 . In: J Biol Chem . 276, No. 37, 2001, pp. 34631-34636. PMID 11457843 .