, Volume 29, Issue 10, pp 999-1011
Date: 27 Sep 2012

Kisspeptins in human reproduction—future therapeutic potential

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Abstract

Objective

Kisspeptins (Kps), were first found to regulate the hypothalamopituitary-gonadal axis (HPG) axis in 2003, when two groups-demonstrated that mutations of GPR54 causes idiopathic hypogonadotropic hypogonadism (IHH) characterized by delayed puberty. Objective of this review is to highlight both animal and human discoveries in KISS1/GPR54 system in last decade and extrapolate the therapeutic potential in humans from till date human studies.

Design

A systematic review of international scientific literature by a search of PUBMED and the authors files was done for Kp in reproduction, metabolic control & signal transduction.

Setting

None

Patient(s): In human studies—normal subjects patients with HH, or HA.

Main outcome measures: Effects of Kp on puberty, brain sexual maturation, regulation of GnRH secretion, metabolic control of GnRH Neurons (N).

Results

Kps/GPR54 are critical for brain sexual maturation, puberty and regulation of reproduction. Kps have been implicated in mediating signals to GnRH N—positive and negative feedback, metabolic input. Ability of Kp neurons to coordinate signals impinging on the HPG axis makes it one of most important regulators of reproductive axis since GnRH N’s lack many receptors, with Kp neurons serving as upstream modulators.

Conclusions

Kps have proven as pivotal regulators of the reproduction, with the ability to integrate signals from both internal and external sources. Knowledge about signaling mechanisms involved in Kp stimulation of GnRH and with human studies has made it possible that therapeutically available Kp agonists/antagonists may be used for treatment of delayed puberty/HH, Hypothalamic amenorrhea and in prevention of spread of malignant ovarian/gonadal malignancies along with uses in some eating disorders.

Capsule

Kisspeptins, Upstreams modulators, influence Hypothalamic-Pituitary-Gonadal (HPG) axis and thus brain sexual maturation, puberty initiation as well as positive and negative feedback control on GnRH/LH release and integrate metabolic inputs with regards to fertility desirable or not nutritionally.