Información del artículo
El gen KiSS-1, identificado inicialmente como un gen supresor de metástasis, codifica una serie de péptidos estructuralmente relacionados, denominados kisspeptinas, capaces de inhibir la progresión de ciertos tumores mediante la activación del receptor acoplado a proteínas G, GPR54. La faceta neuroendocrina del sistema KiSS-1/GPR54 fue descubierta a finales de 2003, cuando sendas publicaciones evidenciaron que las mutaciones inactivadoras del gen GPR54 se asocian a ausencia de pubertad e hipogonadismo hipogonadotropo, tanto en humanos como en roedores. Estas observaciones pusieron de manifiesto el papel clave, previamente insospechado, del sistema KiSS-1 en el control del eje reproductor en general y de los mecanismos de activación de la pubertad en particular, y desencadenaron una intensísima actividad investigadora dirigida a elucidar distintos aspectos (efectos, regulación, mecanismos de acción, interacciones) del papel fisiológico de este sistema en el control neuroendocrino de la reproducción. De hecho, las evidencias experimentales acumuladas en los últimos meses permiten afirmar que el sistema KiSS-1 es un elemento esencial en la regulación del sistema neuronal de la gonadoliberina, y por extensión, del eje reproductor. En el presente trabajo revisaremos algunas de estas observaciones, con especial atención a las que implican al sistema KiSS-1 en el control del desarrollo puberal.
Palabras clave:
KiSS-1
GPR54
Gn-RH
LH
FSH
Pubertad
Hipogonadismo
The KiSS-1 gene was originally identified as a metastasis suppressor gene encoding a number of structurally related peptides, called kisspeptins, that inhibit tumor progression through the G protein-coupled receptor, GPR54. The neuroendocrine facet of the KiSS-1/GPR54 system was discovered at the end of 2003, when two publications reported that loss-of-function mutations of the GPR54 gene were associated with the absence of puberty and hypogonadotropic hypogonadism, both in humans and in rodents.
These seminal findings underscored the pivotal –and previously unsuspected– role of the KiSS-1 system in control of reproduction in general, and in puberty in particular, and have prompted intense research efforts to characterize distinct aspects (effects, regulation, mechanism of action, interactions) of the neuroendocrine physiology of kisspeptins.
Indeed, in the last months, KiSS-1 has been proven to be a major physiological gatekeeper of gonadoliberin (Gn-RH) neurons and, hence, of the reproductive axis. The present review comprehensively describes the major features of the KiSS-1 system, with special emphasis on its putative role as a major regulator of mammalian puberty.
Key words:
KiSS-1
GPR54
Gn-RH
LH
FSH
Puberty
Hypogonadism
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