Plasma Kisspeptin Levels Research Articles

Oral sodium oxybate does not alter plasma kisspeptin levels in healthy male volunteers.

Gamma-hydroxybutyrate (GHB, clinically administrated as sodium oxybate) is a GABA-B/GHB receptor agonist inducing prosexual effects and progesterone secretion in humans. As the neuropeptide kisspeptin has well-established roles in regulating sexual behavior and as it was also associated with GABA-B receptor and progesterone function, we investigated the effect of two GHB doses (20 and 35 mg/kg p.o.) on plasma kisspeptin levels in 30 healthy male volunteers, using a double-blind, randomized, placebo-controlled cross-over design. We found no significant alterations of kisspeptin levels after GHB administration compared to placebo. In conclusion, plasma kisspeptin levels are not related to the prosexual effects of GHB.

Targeting hepatic kisspeptin receptor ameliorates nonalcoholic fatty liver disease in a mouse model.

Nonalcoholic fatty liver disease (NAFLD), the most common liver disease, has become a silent worldwide pandemic. The incidence of NAFLD correlates with the rise in obesity, type 2 diabetes, and metabolic syndrome. A hallmark featureof NAFLD is excessive hepatic fat accumulation or steatosis, due to dysregulated hepatic fat metabolism, which can progress to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Currently, there are no approved pharmacotherapies to treat this disease. Here, we have found that activation of the kisspeptin 1 receptor (KISS1R) signaling pathway has therapeutic effects in NAFLD. Using high-fat diet–fed mice, we demonstrated that a deletion of hepatic Kiss1r exacerbated hepatic steatosis. In contrast, enhanced stimulation of KISS1R protected against steatosis in wild-type C57BL/6J mice and decreased fibrosis using a diet-induced mouse model of NASH. Mechanistically, we found that hepatic KISS1R signaling activates the master energy regulator, AMPK, to thereby decrease lipogenesis and progression to NASH. In patients with NAFLD and in high-fat diet–fed mice, hepatic KISS1/KISS1R expression and plasma kisspeptin levels were elevated, suggesting a compensatory mechanism to reduce triglyceride synthesis. These findings establish KISS1R as a therapeutic target to treat NASH.

Serum kisspeptin, to discriminate between ectopic pregnancy, miscarriage and first trimester pregnancy

The present study aimed to determine serum kisspeptin levels which is an emergent marker regarding trophoblastic invasion, in patients with different types of early pregnancy. We also aimed to investigate whether kisspeptin can be used for differential diagnosis of ectopic pregnancy or miscarriage from early pregnancy. This was a prospective case-control study that was conducted at a tertiary centre of obstetrics and gynaecology. Four groups of women (81 patients) enrolled in the study: group 1, women with ectopic pregnancy (n = 17); group 2, women with miscarriage (n = 23); group 3, women with healthy pregnancy at first trimester (n = 21); and group 4, healthy non-pregnant women (n = 18). Serum kisspeptin levels were found as 0.30 (0.22–0.40), 0.11 (0.08–0.16), 1.48 (1.29–1.80), and 0.03 (0.01–0.04) ng/mL in ectopic, miscarriage, healthy pregnancy and non-pregnant groups, respectively (p< .001). A moderate correlation was seen between serum kisspeptin levels and human chorionic gonadotropin (β-hCG) (r= 0.51, p< .001). Our data showed that for the first time that a single serum kisspeptin level may be used to discriminate ectopic pregnancy or miscarriage from healthy pregnancy at early weeks’ gestation. In addition, serum kisspeptin levels of the patients with ectopic pregnancy were found higher significantly than the patients with miscarriage. Impact Statement What is already known on this subject? Definite diagnosis of abnormal or abnormal pregnancies at first trimester is based on hCG levels and ultrasonography. Kisspeptin, a neuropeptide was investigated in normal pregnancies and found to be increased in trophoblastic invasion. What do the results of this study add? Serum kisspeptin levels in patients with normal pregnancy were found more higher than patients with ectopic or miscarriage at early weeks of gestation (p < .001). The women with ectopic pregnancy have higher kisspeptin levels than the women with miscarriage (p < .001). What are the implications of these findings for clinical practice and/or further research? These findings can be used to make differential diagnosis between abnormal and normal early pregnancies. In future studies with more sample size, serum or plasma kisspeptin levels in early weeks of gestation can be investigated.

Comparison of the Kisspeptin levels in early onset preeclampsia and late-onset preeclampsia.

Maternal Kisspeptin plays role in cell migration which is responsible for trophoblast invasion. We aimed to investigate the role of Kisspeptin as an invasion marker in the early-onset and late-onset preeclampsia cases. In this case-control study, 125 patients were included: 20 patients with early-onset preeclampsia and 20 gestational-age-matched healthy controls; 45 patients with late-onset preeclampsia and 40 gestational-age-matched controls). Maternal plasma Kisspeptin concentration was measured and compared in groups regarding the presence of early-onset and late-onset preeclampsia. In the late-onset PE group, significantly higher maternal plasma Kisspeptin values were observed compared with the control group at > 34weeks of gestation (68.7 ± 93.4pg/ml vs 68.5 ± 57.9pg/ml; p = 0.004). Before the 34th week of gestation, plasma Kisspeptin levels did not show a significant difference when patients with early-onset PE and gestational-age matched controls were compared (66.8 ± 87.9pg/ml vs 48.5 ± 91.3pg/ml; p = 0.56). Plasma Kisspeptin levels were significantly higher in women with late-onset preeclampsia, while no significant difference was observed in early-onset preeclampsia when compared with healthy gestational age-matched controls. The role of Kisspeptin proteins is still not clearly defined in the pathogenesis of preeclampsia.

Growth Hormone (GH) Treatment Decreases Plasma Kisspeptin Levels in GH-Deficient Adults with Prader-Willi Syndrome.

Obesity and growth hormone (GH)-deficiency are consistent features of Prader–Willi syndrome (PWS). Centrally, kisspeptin is involved in regulating reproductive function and can stimulate hypothalamic hormones such as GH. Peripherally, kisspeptin signaling influences energy and metabolic status. We evaluated the effect of 12-month GH treatment on plasma kisspeptin levels in 27 GH-deficient adult PWS patients and analyzed its relationship with metabolic and anthropometric changes. Twenty-seven matched obese subjects and 22 healthy subjects were also studied. Before treatment, plasma kisspeptin concentrations in PWS and obese subjects were similar (140.20 (23.5–156.8) pg/mL vs. 141.96 (113.9–165.6) pg/mL, respectively, p = 0.979)) and higher (p = 0.019) than in healthy subjects (124.58 (107.3–139.0) pg/mL); plasma leptin concentrations were similar in PWS and obese subjects (48.15 (28.80–67.10) ng/mL vs. 33.10 (20.50–67.30) ng/mL, respectively, p = 0.152) and higher (p < 0.001) than in healthy subjects (14.80 (11.37–67.30) ng/mL). After GH therapy, lean body mass increased 2.1% (p = 0.03), total fat mass decreased 1.6% (p = 0.005), and plasma kisspeptin decreased to levels observed in normal-weight subjects (125.1(106.2–153.4) pg/mL, p = 0.027). BMI and leptin levels remained unchanged. In conclusion, 12-month GH therapy improved body composition and decreased plasma kisspeptin in GH deficient adults with PWS. All data are expressed in median (interquartile range).

G protein-coupled kisspeptin receptor induces metabolic reprograming and tumorigenesis in estrogen receptor-negative breast cancer

Triple-negative breast cancer (TNBC) is a highly metastatic and deadly disease. TNBC tumors lack estrogen receptor (ERα), progesterone receptor (PR), and HER2 (ErbB2) and exhibit increased glutamine metabolism, a requirement for tumor growth. The G protein-coupled kisspeptin receptor (KISS1R) is highly expressed in patient TNBC tumors and promotes malignant transformation of breast epithelial cells. This study found that TNBC patients displayed elevated plasma kisspeptin levels compared with healthy subjects. It also provides the first evidence that in addition to promoting tumor growth and metastasis in vivo, KISS1R-induced glutamine dependence of tumors. In addition, tracer-based metabolomics analyses revealed that KISS1R promoted glutaminolysis and nucleotide biosynthesis by increasing c-Myc and glutaminase levels, key regulators of glutamine metabolism. Overall, this study establishes KISS1R as a novel regulator of TNBC metabolism and metastasis, suggesting that targeting KISS1R could have therapeutic potential in the treatment of TNBC.

Roux-en-Y gastric bypass surgery improves hepatic glucose metabolism and reduces plasma kisspeptin levels in morbidly obese patients with type 2 diabetes.

Roux-en-Y gastric bypass surgery (RYGB) is known to improve whole-body glucose metabolism in patients with type 2 diabetes (T2D), although the mechanisms are not entirely clear and are likely multifactorial. The aim of this study was to assess fasting hepatic glucose metabolism and other markers of metabolic activity before and after RYGB in patients with and without T2D. Methods: Metabolic characteristics of patients who are obese with T2D were compared with those without the disease (non-T2D) before and 1 and 6 mo after RYGB. Fasting plasma insulin and the insulin:glucagon ratio were markedly reduced as early as 1 mo after RYGB in both patients with T2D and without T2D. Despite this reduction, endogenous glucose production and fasting plasma glucose levels were lower in both groups after RYGB, with the reductions being much larger in T2D. Plasma kisspeptin, an inhibitor of insulin secretion, was reduced only in T2D after surgery. Improved hepatic glucose metabolism and lower plasma kisspeptin in T2D after RYGB may link improved hepatic function with enhanced insulin responsiveness after surgery.NEW & NOTEWORTHY Our manuscript is the first, to the best of our knowledge, to present data showing that Roux-en-Y gastric bypass surgery (RYGB) lowers fasting kisspeptin levels in patients who are obese with type 2 diabetes. This lowering of kisspeptin is important because it could link improvements in liver glucose metabolism after RYGB with increased insulin responsiveness also seen after surgery.

Evaluation of Kisspeptin Level in Non Obstructive Azoospermic Patients

AbstractBackground: Non-obstructive azoospermia is characterized by the complete absence of sperm in the ejaculate due to testicular failure. One of the genetic causes of non-obstructive azoospermia is the mutations in kisspeptin hormone and the kisspeptin hormone receptor (Kiss1r) genes. The level of kisspeptin hormone has been investigated in patients with non-obstructive azoospermia.Aim of Study: The aim of the study was to evaluate the level of kisspeptin hormone (KISS1) in the serum of non-obstructive azoospermic males and its relation to fertility hormones (Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Testosterone and Prolactin).Patients and Methods: This case control study was done from August 2017 to August 2018 & included 25 non-obstructive azoospermic patients & 25 cases of age matched healthy fertile control subjects. After full history taking and general and local examination, Kisspeptin level was measured using ELISA. Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Testosterone (T) and Prolactin hormone (PRL) were also measured.Results: The mean value of kisspeptin hormone was significantly lower in cases (6.30±2.07ng/ml) than controls (36.70±9.64ng/ml). The patients had significant high level of FSH (p-value <0.001), high level of LH (p-value=0.001) and low level of Testosterone (p-value=0.022). No correlation was found between plasma kisspeptin levels and (FSH, LH, Testosterone & Prolactin).Conclusion: Kisspeptin level is lower in non-obstructive azoospermic infertile males than the fertile controls, so it might be used as a diagnostic tool for infertility and treatment of infertility disorders in patients proved to have a low level of kisspeptin hormone.

Rs4889 polymorphism in KISS1 gene, its effect on polycystic ovary syndrome development and anthropometric and hormonal parameters in Saudi women

BackgroundKisspeptin is involved in female reproduction. This study was designed to i- estimate kisspeptin levels in women with polycystic ovary syndrome (PCOS), in comparison with controls, ii- study the correlations between kisspeptin and PCOS-related reproductive hormones, and iii- investigate the relation between KISS1 gene polymorphisms and hormone levels in women suffering from PCOS.MethodsThe investigation was a clinically designed study on 28 women with PCOS, and 30 normal, healthy women with no signs of PCOS as controls. Blood samples were collected between day 3 and day 6 of the menstrual cycle in both groups at 8:00 a.m., and circulating levels of LH, FSH and kisspeptin were estimated. DNA was extracted from whole blood and all coding exons of KISS1 gene were sequenced.ResultsWomen with PCOS had higher LH levels and BMI compared to controls. Plasma kisspeptin levels were positively correlated with LH levels. There was no statistically significant difference between the groups in terms of kisspeptin and FSH levels. The SNP rs4889 C/G, a non-synonymous SNP, was investigated in the PCOS group. The frequency of GG genotype was significantly higher in the PCOS compared to the controls. These patients were more obese, had higher kisspeptin and FSH levels.ConclusionThe results of the study show that the genetic variation of KISS1 gene may be a factor contributing to PCOS development. The association between the gene and the gene variation and PCOS need further validation in large-scaled and functional studies.

Intra-follicular kisspeptin levels are related to oocyte maturation and gonadal hormones in patients who are undergoing assisted reproductive technology.

PurposeTo assess the kisspeptin concentrations in follicular fluid and their relationship with clinical outcomes during assisted reproductive technology.MethodsThirty‐nine patients who were aged 24‐40 years and underwent oocyte retrieval for in vitro fertilization/intracytoplasmic sperm injection participated in this study. In 65 follicular fluid samples that had been obtained from 30 patients and their blood samples, the kisspeptin levels were measured in order to investigate the correlations with their gonadal hormone levels. Venous blood samples were collected from 14 patients to investigate their plasma kisspeptin levels across different phases of assisted reproductive technology.ResultsThe follicular fluid kisspeptin level was significantly higher than that of the plasma level and was positively associated with the follicular fluid estradiol concentration and with the serum estradiol and number of mature oocytes. In the plasma, the maximum concentration of kisspeptin was observed on the day of ovum pick‐up and on the day of embryo transfer during ovarian stimulation for assisted reproductive technology.ConclusionKisspeptin was present in the follicular fluid and the plasma kisspeptin concentration was affected by ovarian stimulation. Kisspeptin appears to affect oocyte maturation and ovulation.

Plasma kisspeptin levels are associated with insulin secretion in nondiabetic individuals.

To evaluate if plasma kisspeptin concentrations are associated with insulin secretion, as suggested by recent in vitro studies, independently of confounders. 261 nondiabetic subjects were stratified into tertiles according to kisspeptin values. Insulin secretion was assessed using indexes derived from oral glucose tolerance test (OGTT). After adjusting for age, gender, and BMI, subjects in the highest (tertile 3) kisspeptin group exhibited significantly lower values of insulinogenic index, corrected insulin response (CIR30), and Stumvoll indexes for first-phase and second-phase insulin release as compared with low (tertile 1) or intermediate (tertile 2) kisspeptin groups. Univariate correlations between kisspeptin concentration and metabolic variables showed that kisspeptin concentration was significantly and positively correlated with age, blood pressure, and 2-h post-load glucose, and inversely correlated with BMI, and waist circumference. There was an inverse relationship between kisspeptin levels and OGTT-derived indexes of glucose-stimulated insulin secretion. A multivariable regression analysis in a model including all the variables significantly correlated with kisspeptin concentration showed thar age (β = -0.338, P<0.0001), BMI (β = 0.272, P<0.0001), 2-h post-load glucose (β = -0.229, P<0.0001), and kisspeptin (β = -0.105, P = 0.03) remained associated with insulinogenic index. These factors explained 34.6% of the variance of the insulinogenic index. In conclusion, kisspeptin concentrations are associated with insulin secretion independently of important determinants of glucose homeostasis such as gender, age, adiposity, 2-h post-load glucose, and insulin sensitivity.

Kisspeptin Is a Novel Regulator of Human Fetal Adrenocortical Development and Function: A Finding With Important Implications for the Human Fetoplacental Unit.

Context:The human fetal adrenal (HFA) is an integral component of the fetoplacental unit and important for the maintenance of pregnancy. Low kisspeptin levels during pregnancy are associated with miscarriage, and kisspeptin and its receptor are expressed in the HFA. However, the role of kisspeptin in fetal adrenal function remains unknown.Objective:To determine the role of kisspeptin in the developing HFA.Design:Experiments using H295R and primary HFA cells as in vitro models of the fetal adrenal. Association of plasma kisspeptin levels with HFA size in a longitudinal clinical study.Setting:Academic research center and tertiary fetal medicine unit.Participants:Thirty-three healthy pregnant women were recruited at their 12-week routine antenatal ultrasound scan.Main Outcome Measures:The spatiotemporal expression of Kiss1R in the HFA. The production of dehydroepiandrosterone sulfate (DHEAS) from HFA cells after kisspeptin treatment, alone or in combination with adrenocorticotropic hormone or corticotropin-releasing hormone. Fetal adrenal volume (FAV) and kisspeptin levels at four antenatal visits (∼20, 28, 34, and 38 weeks’ gestation).Results:Expression of Kiss1R was present in the HFA from 8 weeks after conception to term and was shown in the inner fetal zone. Kisspeptin significantly increased DHEAS production in H295R and second-trimester HFA cells. Serial measurements of kisspeptin confirmed a correlation with FAV growth in the second trimester, independent of sex or estimated fetal weight.Conclusions:Kisspeptin plays a key role in the regulation of the HFA and thus the fetoplacental unit, particularly in the second trimester of pregnancy.

Plasma kisspeptin levels in lactational amenorrhea

The kisspeptin is a neuropeptide to play physiological roles in regulating gonadotropin-releasing hormone secretion in the hypothalamus. In human plasma, the kisspeptin concentration is measured, but gonadotropin-releasing hormone is not. This study aims to understand the physiological roles of the circulating kisspeptin in lactational amenorrhea in humans because prolactin reduces the kisspeptin expression and luteinizing hormone secretion resulting in anovulations in rodent brains. Plasma kisspeptin levels were measured in 11 subjects in lactational amenorrhea and in four cases with pathological amenorrhea by different etiologies for comparison using the enzyme immunoassay specific for human kisspeptin. The plasma kisspeptin levels in the 11 women with lactational amenorrhea were 15.2 ± 2.5 fmol/mL (mean ± SD) which were not significantly different as compared with 16.5 ± 4.8 fmol/mL (mean ± SD) in four age-matched women with menstrual cycles as we reported previously. In the four cases with pathological amenorrhea, their plasma kisspeptin levels were from 5.8 to 13.7 fmol/mL. This study demonstrated that the plasma kisspeptin levels were not totally reduced in lactational or pathological amenorrhea. These results suggest the physiological roles of the circulating kisspeptin are different from the role in the brain.

Association between plasma kisspeptin levels and adolescent gynecomastia.

Gynecomastia is defined as benign proliferation of male breast glandular tissue. To date, the pathophysiology of adolescent gynecomastia (AG) remains unclear. Kisspeptin is a polypeptide that plays an important role in the regulation of the hypothalamic-pituitary-gonadal hormonal axis. In this study, we investigated whether there is a relationship between kisspeptin and AG. This study included 40 males between 9 and 18 years of age diagnosed with gynecomastia. The control group consisted of 30 young healthy males in the same age range. The participants were evaluated with respect to anthropometric measurements (age, height, body weight, body mass index, breast and pubic stages and testicular volume). The levels of kisspeptin, follicle-stimulating hormone, luteinizing hormone, estradiol (E2), testosterone (T), and ratio of E2 to T were measured in both groups. The mean age was 13.8 years. There were no differences between the groups in terms of anthropometric parameters, plasma gonadotropin levels, estrogen levels, and E2/T (P > 0.05). Plasma kisspeptin (0.77 and 0.54 ng/mL, P < 0.05) and T (253.9 ng/dL and 117.9 ng/dL) levels were significantly higher in the AG group than in the control group (P < 0.001). Kisspeptin levels are an important factor in AG.

Plasma Kisspeptin Levels in Newborn Infants with Breast Enlargement.

Objective: Kisspeptin levels have been reported in children with premature thelarche, precocious puberty and adolescent gynecomastia, but there are no reports on kisspeptin levels in the neonatal period. This study aimed to investigate plasma kisspeptin hormone levels in newborns with and without breast enlargement.Methods:Plasma kisspeptin levels and other related biochemical variables were investigated in this prospective study conducted on 40 (20 girls and 20 boys) newborn infants with breast enlargement and on 40 healthy control infants (20 girls and 20 boys). Two-milliliter venous blood samples were taken in hemogram tubes with K2EDTA. Kisspeptin assays were performed using the enzyme-immunoassay method.Results:Mean plasma kisspeptin levels were 0.6±0.2 ng/mL in the study group and 0.5±0.2 ng/mL in the control group. Plasma kisspeptin concentrations were significantly higher in the study group (p=0.039) and also showed a correlation with serum prolactin levels (p=0.006). Significant correlations were also determined between plasma kisspeptin and luteinizing hormone concentrations (p=0.05, r=0.312).Conclusion:The findings of this study suggest that plasma kisspeptin and serum prolactin levels may be involved in the physiopathology of breast enlargement in newborns.

Determination of plasma kisspeptin concentrations during reproductive cycle and different phases of pregnancy in crossbred cows using bovine specific enzyme immunoassay

Kisspeptin, a decapeptide and potent secretagogue of GnRH has been emerged recently as a master player in the regulation of reproduction in animals. Determination of kisspeptin in peripheral circulation is, therefore, very important for studying the control of its secretion and its role on reproduction in bovine species, the information on which is not available during any physiological state in this species, may probably be due to non-availability of simple assay procedure to measure the hormone. Therefore, the objective of this study was to develop and validate a simple and sufficiently sensitive enzyme immunoassay (EIA) for kisspeptin determination in bovine plasma using the biotin–streptavidin amplification system and second antibody coating technique. Biotin was coupled to kisspeptin and used to bridge between streptavidin-peroxidase and the immobilized kisspeptin antiserum in the competitive assay. The EIA was conducted directly in 100μl of unknown bovine plasma. Kisspeptin standards ranging from 0.01 to 25.6ng/100μl/well were prepared in hormone-free plasma. The lowest detection limit was 0.1ng/ml plasma. Plasma volumes for the EIA, viz., 50, 100 and 200μl did not influence the shape of standard curve even though a drop in OD450 was seen with higher plasma volumes. A parallelism test was carried out to compare the endogenous bovine kisspeptin with kisspeptin standard used. It showed good parallelism with the kisspeptin standard curve. For the biological validation of the assay, plasma kisspeptin was measured in blood samples collected from six non-lactating cyclic cows during entire estrous cycle and from 18 pregnant cows during different stages of pregnancy. The mean plasma kisspeptin concentration during different days of the estrous cycle was different (P<0.001). Three peaks of kisspeptin were recorded, one on a day before appearance of preovulatory LH surge, second at day 6 and third one at day 18 of the estrous cycle. Plasma kisspeptin concentrations increased (P<0.001) from first through last trimester of pregnancy. Kisspeptin concentrations were also measured in different follicular, luteal and placental tissues. Follicular and placental kisspeptin levels increased (P<0.01) during follicular development and with the advancement of pregnancy, respectively. On the other hand, luteal concentrations of kisspeptin decreased (P<0.01) with its developmental process. In conclusion, a simple, sufficiently sensitive and direct EIA procedure has been developed for the first time to determine plasma kisspeptin levels in bovine. A wide range of kisspeptin concentrations can be detected during different physiological stages in bovine using this kisspeptin–EIA procedure.

Test on kisspeptin levels in girls with idiopathic central precocious puberty and its significance

The aim of this study was to explore the signifi - cance of plasma kisspeptin levels in diagnosis and therapeutic evaluation through the analysis of the kisspeptin levels of girls diagnosed with idiopathic central precocious puberty (ICPP) prior to treatment and after 6-months of treatment and those with simple premature thelarche (PT). A total of 70 girls including 24 girls diagnosed with ICPP, 21 girls with PT and 25 normal girls were enrolled in the study. ELISA analysis was conducted to detect the plasma levels of kisspeptin. The kisspeptin level of the ICPP group prior to treatment (1.80±0.13 ng/ml) was significantly higher than those of the other two groups. The kisspeptin level of the ICPP group after 6 months of treatment (1.49±0.21 ng/ml) was signifi - cantly lower than that prior to treatment (P<0.05). It may be concluded that the plasma level of kisspeptin is associated with the initiation of pubertal development, and it may serve as an important parameter in the diagnosis of ICPP and the evalua- tion of therapeutic effects.

Testing of kisspeptin levels in girls with idiopathic central precocious puberty and its significance.

The aim of this study was to explore the significance of plasma kisspeptin levels in diagnosis and therapeutic evaluation through the analysis of the kisspeptin levels of girls diagnosed with idiopathic central precocious puberty (ICPP) prior to treatment and after 6-months of treatment and those with simple premature thelarche (PT). A total of 70 girls including 24 girls diagnosed with ICPP, 21 girls with PT and 25 normal girls were enrolled in the study. ELISA analysis was conducted to detect the plasma levels of kisspeptin. The kisspeptin level of the ICPP group prior to treatment (1.80±0.13 ng/ml) was significantly higher than those of the other two groups. The kisspeptin level of the ICPP group after 6 months of treatment (1.49±0.21 ng/ml) was significantly lower than that prior to treatment (P<0.05). It may be concluded that the plasma level of kisspeptin is associated with the initiation of pubertal development, and it may serve as an important parameter in the diagnosis of ICPP and the evaluation of therapeutic effects.

The relationship between circulating kisspeptin and sexual hormones levels in healthy females

The kisspeptin (metastin) is an endogenous peptide, which regulates human reproduction by modulating gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin was detected in peripheral blood, although GnRH was not. Previously, we measured plasma kisspeptin levels in male healthy subjects and patients with hypogonadism using enzyme immunoassay (EIA) to elucidate a normal range in healthy males and clinical implications of kisspeptin in male hypogonadism. We suggested that the plasma kisspeptin levels were received feedback from testosterone. In this study, we focused female subjects and elucidated the relationship between menstrual cycle and plasma kisspeptin levels to understand kisspeptin-hypothalamic-pituitary-gonadal axis. We measured plasma kisspeptin levels in eight female volunteers. The plasma kisspeptin levels in female are significantly higher than those in male. There are no significant correlation between plasma kisspeptin levels and sexual hormones. We revealed that the kisspeptin might stimulate a start of menstruation as a trigger, and progress menstruation covered for weakened ovarian function. We suggest that kisspeptin may be closely related with menstrual cycle and that the measurement of plasma kisspeptin levels is useful for understanding of reproductive system.

Reduced levels of plasma kisspeptin during the antenatal booking visit are associated with increased risk of miscarriage.

Context:Kisspeptin is a recently identified hormone encoded by the KISS1 gene, playing a critical role in human reproduction. Plasma kisspeptin levels rise dramatically during normal pregnancy due to placental synthesis, which implicates it as a potential tool for assessing risks of pregnancy complications. No previous prospective study has investigated the association between plasma kisspeptin and risk of miscarriage.Objective:The objective of the study was to determine whether a single plasma kisspeptin or serum human chorionic gonadotropin (hCG) measurement in asymptomatic women attending their booking antenatal visit is associated with miscarriage.Design:This was a prospective cohort study.Setting:The study was conducted at a tertiary obstetric center.Participants:A total of 993 asymptomatic pregnant women with a gestation of 6 weeks or longer attending routine antenatal booking visit were recruited between January 2010 and December 2012.Main Outcome Measures:Plasma kisspeptin and serum hCG were measured during the antenatal booking visit. Pregnancy outcome was recorded prospectively.Results:Plasma kisspeptin correlated with gestation (r2 = 0.57; P < .0001). Gestational age-corrected (multiples of median) plasma kisspeptin was 60.4% lower (P < .001), and multiples of median-hCG was 36.1% lower (P < .001) in women later diagnosed with miscarriage compared with women without miscarriage. Increased plasma kisspeptin was associated with reduced miscarriage risk, even after adjusting for age, body mass index, gestational age, smoking, and blood pressure [odds ratio 0.13 (95% confidence interval 0.08–0.22), P = .0001]. Kisspeptin had a higher diagnostic performance for miscarriage than hCG (receiver-operator characteristic-area under the curve 0.899 ± 0.025 plasma kisspeptin; 0.775 ± 0.040, serum hCG, P < .01 vs plasma kisspeptin).Conclusion:Our data suggest for the first time that a single plasma kisspeptin measurement taken during the antenatal booking visit provides a potential novel marker for identifying asymptomatic pregnant women at a gestation of 6 weeks or greater at increased risk of miscarriage.