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Journal of Assisted Reproduction and... Oct 2012Kisspeptins (Kps), were first found to regulate the hypothalamopituitary-gonadal axis (HPG) axis in 2003, when two groups-demonstrated that mutations of GPR54 causes... (Review)
Review
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.
Topics: Animals; Brain; Feedback, Physiological; Follicular Phase; Gonadotropin-Releasing Hormone; Humans; Hypogonadism; Hypothalamus; Kisspeptins; Male; Mutation; Neurons; Puberty; Receptors, G-Protein-Coupled; Receptors, Kisspeptin-1; Sexual Maturation
PubMed: 23015158
DOI: 10.1007/s10815-012-9856-1 -
European Journal of Obstetrics,... May 2021This systematic review and meta-analysis aimed to summarize the available evidence regarding circulating kisspeptin and anti-müllerian hormone (AMH) and the homeostasis... (Meta-Analysis)
Meta-Analysis
Circulating kisspeptin and anti-müllerian hormone levels, and insulin resistance in women with polycystic ovary syndrome: A systematic review, meta-analysis, and meta-regression.
OBJECTIVE
This systematic review and meta-analysis aimed to summarize the available evidence regarding circulating kisspeptin and anti-müllerian hormone (AMH) and the homeostasis model assessment of insulin resistance (HOMA-IR) index in adolescents and women with and without polycystic ovary syndrome (PCOS).
METHOD
We performed a comprehensive literature search in Medline, Embase, Cochrane, Scopus, and Web of Science for studies evaluating circulating kisspeptin levels in women with and without PCOS published until September 24th, 2020. Co-primary outcomes were the HOMA-IR index and AMH. The quality of included studies was assessed using the Newcastle-Ottawa Scale. Random-effects models were used to estimate outcomes, and effects reported as mean difference (MD) or standardized MD (SMD) and their 95 % confidence interval (CI). The systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42020205030.
RESULTS
We evaluated 18 studies including, 1282 PCOS cases and 977 controls. Participants with PCOS were younger (MD = -2.38 years, 95 %CI -4.32 to -0.44), with higher BMI (MD = 1.16, 95 % CI 0.54-1.78), waist-to-hip ratio (MD = 0.04, 95 %CI 0.02 to 0.05), circulating kisspeptin (SMD = 1.15, 95 %CI 0.68-1.62), luteinizing hormone (SMD = 1.29, 95 %CI 0.76-1.83), AMH (SMD = 0.97, 95 %CI 0.60-1,34), total testosterone (SMD = 2.48, 95 %CI 1.73-3.23), free testosterone (SMD = 1.37, 95 %CI 0.56-2.17), and dehydroepiandrosterone sulphate (SMD = 0.72, 95 %CI 0.32-1.13) levels, and Ferriman-Gallwey score (SMD = 5.08, 95 %CI 2.76-7.39), and lower sex hormone-binding globulin level (SMD = -1.34, 95 %CI -2.15 to -0.52). Besides, participants with PCOS had higher HOMA-IR index (SMD = 0.76, 95 %CI 0.35-1.17), and circulating insulin (SMD = 0.75, 95 %CI 0.30-1.19), leptin (SMD = 2.82, 95 %CI 1.35-4.29), and triglycerides (SMD = 2.15, 95 %CI 1.08-3.23) levels than participants without the syndrome. The meta-regression did not identify significant factors influencing circulating kisspeptin.
CONCLUSION
Patients with PCOS showed higher kisspeptin, LH, insulin, AMH, and androgen levels and HOMA-IR index, and lower sex hormone-binding globulin levels than those without the syndrome.
Topics: Adolescent; Anti-Mullerian Hormone; Female; Humans; Insulin Resistance; Kisspeptins; Polycystic Ovary Syndrome
PubMed: 33744505
DOI: 10.1016/j.ejogrb.2021.03.007 -
Hormone Research in Paediatrics 2020Kisspeptin (KP) is a key player in the regulation of the release of gonadotropin-releasing hormone (GnRH), which increases the secretion of gonadotropin during puberty... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
Kisspeptin (KP) is a key player in the regulation of the release of gonadotropin-releasing hormone (GnRH), which increases the secretion of gonadotropin during puberty to establish reproductive function and regulate the hypothalamic-pituitary-gonadal axis. Premature activation of GnRH secretion leads to idiopathic/central gonadotropin-dependent precocious puberty (CPP). We aimed to compare the blood KP concentrations in girls with CPP and healthy controls.
METHODS
A systematic review and meta-analysis was performed. We searched MEDLINE, EMBASE, The Cochrane Library, and SciELO. Random-effects model and standardized mean difference (SMD) were used. Heterogeneity was assessed through I2. Meta-regression considered patient age, KP fraction, and analytical method for KP measurement.
RESULTS
The 11 studies included comprised 316 CPP patients and 251 controls. Higher KP levels in the CPP group were found (SMD 1.53; CI 95% = 0.56-2.51). Subgroup analysis revealed association with patient age (p = 0.048), indicating a positive correlation between elevation in KP concentration and age in CPP group. A group of patients with precocious thelarche (PT) from 5 of the included studies comprising 121 patients showed higher levels of KP (1.10; -0.25-2.45: CI 95%) and high heterogeneity (I2 = 91%). The CPP/PT ratio for KP level indicates KP 36% higher on CPP than PT patients.
CONCLUSIONS
A consistent difference in KP levels between girls with CPP and controls was identified. While there are important limitations in KP assays which argue against its use as a diagnostic tool, the KP levels in CPP versus control and PT children are consistent with the predicted mechanisms and pathophysiology of CPP.
Topics: Case-Control Studies; Child; Female; Humans; Kisspeptins; Puberty, Precocious
PubMed: 33887744
DOI: 10.1159/000515660 -
The Journal of Maternal-fetal &... Dec 2023A highly accurate serum marker for predicting viable pregnancy needs to be developed. Recent studies have demonstrated that kisspeptin is a potential biomarker for this...
OBJECTIVE
A highly accurate serum marker for predicting viable pregnancy needs to be developed. Recent studies have demonstrated that kisspeptin is a potential biomarker for this purpose.
METHODS
This systematic review evaluated the available data in the literature on the role of kisspeptin as a miscarriage biomarker. A literature search was conducted in the PubMed/Medline, Embase, Web of Science, and Scopus databases using the following keywords: (kisspeptin) AND (miscarriage OR pregnancy loss OR spontaneous abortion OR reproductive failure).
RESULTS
Seven case-control studies were selected for the systematic review. The included papers described the potential role of kisspeptin as a putative biomarker of pregnancy loss. Furthermore, two studies reported that changes in kisspeptin levels may be associated with unexplained infertility and low rates of embryo implantation in women undergoing assisted reproductive technology.
CONCLUSION
Kisspeptin might be used as a potential biomarker of pregnancy viability in the near future. However, studies with better evidence are needed to establish the applicability of kisspeptin as a diagnostic and prognostic tool.
Topics: Pregnancy; Female; Humans; Abortion, Spontaneous; Kisspeptins; Infertility; Reproductive Techniques, Assisted; Biomarkers; Pregnancy Rate; Live Birth; Fertilization in Vitro
PubMed: 37015836
DOI: 10.1080/14767058.2023.2197097