Kisspeptin Dosing Protocol: Fertility Research Guide

Author Correction: Kisspeptin-10 binding to Gpr54 in osteoclasts prevents bone loss by activating Dusp18-mediated dephosphorylation of Src. (Nature communications, 2025)

Limitations: Animal study only — human translation uncertain.

Silencing SIRT1 abolished the protective effects of Kp-10, highlighting the essential role of SIRT1 in its anti-senescence action. These findings suggest that Kp-10 may be a promising therapeutic strategy for OA by mitigating chondrocyte senescence and improving cellular function by modulating the SIRT1 and p53/p21 pathways.

Limitations: No placebo control reported.

We found that KP-10 levels were reduced in both CA patients and mouse models. In CA mice, Gpr54 expression in the Circle of Willis (COW) was also decreased.

Limitations: No placebo control reported.

These findings indicate that KP-10 plays a crucial role in suppressing EC progression and represents a promising therapeutic target for clinical treatment. However, more comprehensive studies are needed to fully elucidate the underlying mechanisms and explore the clinical potential of KP-10 in EC therapy.

Limitations: No placebo control reported.

Using the validated confirmation procedure, a black-market vial of kisspeptin-10 was analysed. The product contained no unexpected impurities, although it appeared to have undergone more degradation than the purchased reference standard.

Limitations: No placebo control reported.

Kiss1, Gpr54 and Dusp18 knockout mice all exhibit osteoclast hyperactivation and bone loss, and Kp-10 abrogated bone loss by suppressing osteoclast activity in vivo. Therefore, Kp-10/Gpr54 is a promising therapeutic target to abrogate bone resorption by Dusp18-mediated Src dephosphorylation.

Limitations: Animal study only — human translation uncertain.

Augmentation of collagen deposition by KiSS-10 is dependent on the protein synthesis elevation, inhibition of MMPs activity (increase of TIMPs release) or decrease of MMPs concentration. The profibrotic activity of KiSS-10 is mediated by FAK and is not dependent on TGF-β1.

Limitations: No placebo control reported.

Consistent with these observations, KP-10 treatment further diminished α-syn and ChAT immunoreactivity in neurons overexpressing wild-type and E46K mutant α-syn. Overall, these findings lend additional credence to the previous notion that KP-10's binding zone may harness efficacious moieties of neuroprotective intent.

Limitations: No placebo control reported.

The findings of our study suggest the effects of KISS on basic ovarian functions. We also observed the influence of BTC on these functions and its ability to modify the effects of KISS on these processes.

Limitations: Animal study only — human translation uncertain.

Understanding the influence of kisspeptin on the reproductive axis and related mechanisms will help the future application of kisspeptin in disease diagnosis and treatment. In this review, we critically appraise the role of kisspeptin in the HPG axis, including its signaling pathways, negative and positive feedback mechanisms, and its control on female and male reproduction.

Limitations: No placebo control reported. Review article — no new primary data.

Supra-vital plasma membrane integrity (%), viable sperm with intact acrosome (%) and DNA integrity (%) were improved (p&#x2009;<&#x2009;0.05) with all doses of kisspeptin-10 as compared to negative control. It was concluded that the addition of 15 and 20&#x2009;&#x3bc;mol&#x2009;L-1 kisspeptin-10 in cryodiluent ameliorated the overall frozen-thawed quality parameters of Nili-Ravi buffalo spermatozoa.

Limitations: Animal study only — human translation uncertain.

Meanwhile, results of dual-luciferase reporter assays indicated that miR-1246 targeted the 3'UTR of StAR in BGCs. These results demonstrated that kp-10 induced P4 synthesis in BGCs by promoting free cholesterol transport via regulating expression of miR-1246/StAR.

Limitations: Animal study only — human translation uncertain.

There were also no KP-10-related findings observed in recovery animals on Day 29. In conclusion, KP-10 demonstrated favorable safety profile in dog where 1,000&#xa0;&#x3bc;g/kg dose was considered as a no-observed-adverse-effect level dose when administered IV once daily for 14&#xa0;days.

Limitations: Animal study only — human translation uncertain.

E2 showed two peaks, at 90&#x2011;120 days and 240&#x2011;270 days. The trends in Kp&#x2011;10 and GnIH concentrations suggest that these two hormones might act to maintain the delicate endocrine equilibrium of pregnancy.

Limitations: Animal study only — human translation uncertain.

Moreover, the total numbers of piglets born and those born alive did not differ among the three groups. These findings suggested that 0.5&#x202f;mg KP-10 given at 96&#x202f;h after weaning could be used in FTAI programmes to manage batch farrowing in sows.

Limitations: Animal study only — human translation uncertain.

Human studies have demonstrated associations between circulating kisspeptin levels and measures of insulin secretion and insulin resistance; and the only published interventional study has confirmed kisspeptin enhances glucose-stimulated insulin secretion in humans. Further studies are required to elucidate the mechanisms underlying the effects of kisspeptin on the pancreatic &#x3b2;-cell and to determine the therapeutic potential of kisspeptin receptor agonist in the treatment of disorders of glucose homeostasis.

Limitations: No placebo control reported. Review article — no new primary data.

This meta-analysis finally included 12 studies. Compared with controls, women with PCOS showed significantly increased circulatory KISS-1 levels (SMD&#x202f;=&#x202f;0.47; P&#x202f;=&#x202f;0.002).

Limitations: No placebo control reported. Review article — no new primary data.

These results demonstrate that BMP2 protein has an autocrine effect upon KP-10 treatment. Taken together, these findings suggest that KP-10/GPR54 signaling induces osteoblast differentiation via NFATc4-mediated BMP2 expression.

Limitations: Animal study only — human translation uncertain.

Furthermore, KISS1R mRNA also decreased in the luteinized human granulosa cells of high-risk OHSS patients, and was consistent with the results in rat models and HUVECs. In conclusion, Kp-10 prevents the increased VP of OHSS by the activation of KISS1R and the inhibition of VEGF.

Limitations: No placebo control reported.

In summary, these findings suggest that kisspeptin-10 could alter the morphology and structure of myocardial cells, serum metabolite levels, and expression of genes and proteins in heart tissues. Our work determined the profound effects of kisspeptin-10 on the heart, which could further lead to the development of therapeutics related to kisspeptin-10, including antagonists and analogs.

Limitations: Animal study only — human translation uncertain.

These results suggest that chronic administration of kisspeptin analogs disrupts endogenous kisspeptin signals to suppress intrinsic GnRH pulses, perhaps by attenuating GnRH-neural response and inducing continuous GnRH leakage from the hypothalamus. The potential utility of kisspeptin analogs as novel agents to treat hormone-related diseases, including prostate cancer, is discussed.

Limitations: Animal study only — human translation uncertain.

In addition, 60 min postinjection, 0.15 nmol [dY](1)KP-10 significantly increased total testosterone levels in mice whereas the same dose of KP-10 had no significant effect. Should manipulation of the kisspeptin/KISS1R signaling system prove therapeutically useful, long-lasting analogs such as [dY](1)KP-10 may have greater therapeutic potential than endogenous forms of kisspeptin.

Limitations: No placebo control reported.

The other, located in the hypothalamic arcuate nucleus, appears to be involved in generating GnRH pulses, resulting in luteinising hormone pulses followed by follicular development and steroidogenesis in the ovary. The present review focuses on the physiological role of the two populations of kisspeptin neurones in controlling gonadal functions by generating the two modes of GnRH release in a female rat model.

Limitations: Animal study only — human translation uncertain. Review article — no new primary data.

Thus, the ARC population of metastin/kisspeptin neurons is a target of estrogen negative feedback action on tonic GnRH release. The lactating rat model provided further evidence indicating that ARC metastin/kisspeptin neurons are involved in GnRH pulse generation, because pulsatile release of luteinizing hormone (LH) is profoundly suppressed by suckling stimulus and the LH pulse suppression is well associated with the suppression of ARC metastin/kisspeptin and KiSS-1 gene expression in lactating rats.

Limitations: Animal study only — human translation uncertain.

Expression of Gpr54 and Kiss1 have also been reported in several peripheral tissues including the pituitary, ovary, testes and the placenta raising the possibility that these genes may have additional functions in these tissues. Regulation of kisspeptin expression by peripheral factors such as leptin may be involved in coordinating metabolic status with the reproductive axis.

Limitations: No placebo control reported. Review article — no new primary data.

GnRH neurons express mRNA for GPR54, a metastin/kisspeptin receptor, and have a close association with metastin/kisspeptin neurons at the cell body and terminal level, but the precise mechanism by which this peptide regulates the two modes of GnRH release needs to be determined. Metastin/kisspeptin, therefore, is a key hypothalamic neuropeptide, which is placed immediately upstream of GnRH neurons and relays the peripheral steroidal information to GnRH neurons to control estrous cyclicity.

Limitations: Animal study only — human translation uncertain. Review article — no new primary data.

Various doses of metastin (kisspeptin-54) (0.02, 0.2, and 2 nmol) injected into the third ventricle caused a significant increase in LH secretion in both lactating and nonlactating OVX rats, suggesting that lactating rats are responsive to metastin (kisspeptin-54) stimulus. Thus, the present study demonstrated that KiSS-1 mRNA/metastin (kisspeptin-54) expression is inhibited in the ARC by the suckling stimulus, suggesting that the inhibition is most probably involved in suppressing LH secretion in lactating rats.

Limitations: Animal study only — human translation uncertain.

In addition, the hypothalamic KiSS-1/GPR54 system has been proven as an essential gatekeeper of GnRH neurons, involved in their activation at puberty and their regulation by gonadal steroids and (probably) metabolic factors. This review comprehensively examines the experimental evidence obtained to date supporting a pivotal role of kisspeptins and GPR54 in the control of reproduction.

Limitations: No placebo control reported. Review article — no new primary data.

Production of metastin and, to a lesser extent, GPR54 are negatively regulated by testosterone and oestrogen, and injecting GPR54 ligands can increase hormone secretion in rodents. Thus, GPR54 is required for normal functioning of the hypothalamic-pituitary-gonadal axis, probably at the level of gonadotrophin-releasing-hormone secretion.

Limitations: No placebo control reported. Review article — no new primary data.

Suppressed motility was paralleled with suppressed gelatinolytic activity of isolated trophoblasts. These results identified Kp-10 as a novel paracrine/endocrine regulator in fine-tuning trophoblast invasion generated by the trophoblast itself.

Limitations: No placebo control reported.