Kisspeptin is a principal permissive neurotransmitter for the reproductive brain: by depolarizing GnRH neurons it translates estrogen, metabolic and circadian cues into a surge in LH which promotes ovulation and its own expression is simultaneously sculpted by sex-steroid negative feedback. As such it provides a physiologic handle for researchers to restore or otherwise tune fertility while maintaining the hypothalamic pulse generator.
Fig. 1 The role of kisspeptin in embryo implantation. Successful implantation requires communication between the blastocyst and a receptive uterine epithelium.1,5
Kisspeptin neurons in the arcuate nucleus and the anteroventral periventricular nucleus (AVPV) create the final common relay where metabolic, steroid, and photic information converges on the dispersed GnRH cell bodies. GPR54 activation by kisspeptin ligand initiates a signalling cascade that is dominated by Gαq-phospholipase C, resulting in diacylglycerol-induced inhibition of K_ATP channels and concurrent activation of canonical transient receptor potential channels. The resultant membrane depolarization is sufficient to induce burst firing of GnRH axons and to be faithfully communicated as pulsatile peptide release into the hypophyseal portal blood. Because kisspeptin neurons also co-express neurokinin B and dynorphin, an auto-regulatory triad (KNDy) is created where neurokinin B provides autocrine excitation, dynorphin provides intermittent restraint and kisspeptin relays the integrated output to GnRH terminals. This architecture enables estrogen to provide both negative and positive feedback on GnRH/LH secretion: low concentrations of estrogen result in the inhibition of arcuate kisspeptin transcription (negative feedback), whereas rising levels of follicular-phase estrogen stimulate kisspeptin expression periventricularly and thereby induce the GnRH/LH surge (positive feedback). The system is inherently frequency-coded so that high-amplitude kisspeptin volleys favor LH secretion, while lower-frequency pulses more preferentially drive FSH secretion thereby preserving the gonadotropin ratio necessary for follicular development. It is critical to note that the peptide is not a continuous drive, but instead is expressed in a temporally patterned manner that is gated by leptin, insulin and circadian pacemakers ensuring that the drive to attempt reproductive activity only occurs when the metabolic and temporal milieu are permissive. These features have made kisspeptin the preferred pharmacologic probe with which to reinstate GnRH pulsatility in states of functional hypothalamic amenorrhoea, to synchronize follicular waves in preparation for assisted conception and to dissect the neural origins of anovulatory disorders such as polycystic ovary syndrome.
Fig. 2 Schematic diagram showing how kisspeptin regulates hypothalamus-pituitary-ovary axis in rodents and humans.2,5
Activation of GnRH neurons is accomplished by a well-orchestrated ion-channel dance that transforms the transient ligand/receptor interaction into a long-lasting electrical event. GPR54 is G protein–coupled to Gαq/11. This interaction can activate phospholipase Cβ and its downstream target, the inositol trisphosphate receptor, found in thapsigargin-sensitive Ca2+ stores. This causes a release of Ca2+ from the stores and activation of protein kinase C isoforms. The activation of the PKC isoforms phosphorylates ATP-sensitive potassium channels, leading to closure of the channel; depolarization from this event activates low-threshold T-type calcium channels that initiate high-frequency spiking. Concomitant inhibition of inwardly rectifying potassium conductances prolongs the duration of the plateau so that neuropeptide-containing vesicles at the axon terminal can be exposed to the depolarizing Ca2+ influx for sufficient time for exocytosis. In the interconnected GnRH neuron network, electrical coupling via dendritic bundling means that an action potential induced by kisspeptin in one neuron can spread to neighbors and synchronize the entire group into a synchronized volley which will be recognized as an LH pulse downstream. Estrogen positively regulates this process by up-regulating both GPR54 transcript levels as well as the very calcium channels that are ultimately responsible for carrying out kisspeptin's orders. As a result, the GnRH neuron is prepared to produce a much bigger response at the time of positive feedback. However, the excitatory effect is self-limiting: prolonged receptor stimulation leads to internalization into a recycling endosome compartment. This reversibility has made kisspeptin infusion a preferred way to artificially generate physiological GnRH patterns in patients with hypothalamic amenorrhoea and to map the frequency-response relationship that regulates normal ovarian cyclicity.
In the ovulatory mechanism, kisspeptin is the conductor of the hypothalamus, where slowly increasing levels of follicular-phase estrogen are transformed into a sudden neuroendocrine climax. In the early stages of follicular development, negative feedback from the low levels of estrogen on arcuate kisspeptin neurons (KNDy neurons) is responsible for a GnRH pulse frequency that promotes FSH secretion and encourages follicle growth. A rise in estradiol, in turn, deserts arcuate neurons for the anteroventral periventricular (AVPV) kisspeptin population, where it transcriptionally activates Kiss1 and triggers a massive spike in synthesis of the peptide. This kisspeptin outpouring into the hypophyseal portal system then initiates the high-frequency, high-amplitude pulses of GnRH, which are interpreted by the anterior pituitary gland as a signal to produce the pre-ovulatory LH surge. The kisspeptin positive-feedback mechanism is thus an estrogen-triggered, self-limiting, and inherently amplified neuroendocrine loop because kisspeptin neurons express estrogen receptor-α, and its circadian gating means the surge can only occur within a narrow time window. This mechanism has evolved to couple ovulation with conditions of peak metabolic and photic status. Interruption of this sequence, whether by poor nutrition, over-exercising, or functional abnormalities in the kisspeptin receptor (GPR54), results in anovulation with continuous low LH pulsatility and follicular arrest. Conversely, administration of kisspeptin can induce an LH surge in subjects with functional hypothalamic amenorrhea, allowing for resumption of regular menses in the absence of exogenous gonadotropins. The peptide does not override the ovarian feedback mechanism but rather restores physiological feedback on the hypothalamus, thus maintaining the dynamic range that is required for corpus luteum function and subsequent luteal-phase steroidogenesis. This has made it a physiologic trigger for final oocyte maturation in assisted-conception procedures and a diagnostic probe to determine whether a patient's anovulation is hypothalamic or pituitary in origin.
This sex-specific organization of kisspeptin occurs within a perinatal critical period which ultimately leads to sex-specific oestrogen sensitivity and surge ability. In females, perinatal androgen spares a rostral periventricular population of neurons, which are oestrogen receptor-α rich, from androgen exposure during this period. These neurons are thus sensitive to the increase in follicular-phase oestradiol and can result in a pulse of Kiss1 transcription necessary for the LH surge. In males, this region is organized into an oestrogen non-responsive region by perinatal testosterone, which shunts steroid feedback control of LH to the arcuate nucleus, where kisspeptin expression is inhibited by oestradiol, hence the inability to produce a surge and maintaining tonic LH secretion. This is why females are able to produce an ovulation-inducing kisspeptin surge in adulthood but males are not, and also why perinatal androgen disruption of this system results in a feminized surge mechanism in genetic males. Neonatal deletion or overexpression of kisspeptin in mice also changes the age of pubertal onset and alters adult reproductive behavior, suggesting kisspeptin is not only an activation signal but an instructive signal as well.
So far in modern reproductive medicine, the standout has been in using kisspeptin physiologically, rather than pharmacologically. It is more of a "nudge" than a shove; the treatment re-engages the patient's own hypothalamic pulse generator, allowing follicles to mature and ovulate without the multi-follicular over-drive that's typical of most gonadotropin protocols. By inducing an endogenous GnRH surge (and so LH surge), the peptide provides a time-limited stimulus that can be titrated to the diameter of the leading follicle, and so is a more "monofollicular-friendly" approach to both assisted-conception cycles and spontaneous conception attempts in hypothalamic amenorrhoea. The surge, moreover, is self-limited; as the ligand is cleared, the luteal phase is then free to play out in the restraint of native steroid feedback (not under the prolonged agonist effect of an exogenous hCG, as would be the case following a traditional IVF cycle). This property has fuelled excitement in high-risk populations for whom OHSS is still a life-threatening risk. There has also been parallel work in male infertility, using kisspeptin to recouple pulsatile LH secretion with the circadian clock, and so restore testicular steroidogenesis and sperm quality in states of functional hypogonadism, but without the azoospermia that will follow high-dose testosterone replacement. Taken together, these areas of inquiry are framing kisspeptin not so much as a replacement for existing drugs, but as a mechanistic probe that can identify where the fertility signal is broken, along the hypothalamic–pituitary–gonadal chain, and then selectively repair that link while leaving the rest of the axis free to self-regulate.
In assisted reproduction, kisspeptin is being developed as an alternative ovulation trigger, one that mimics the mid-cycle surge but that does not commit the ovary to the extended luteotrophic stimulus of hCG. Given as a single bolus after standard gonadotropin stimulation and GnRH-antagonist down-regulation, kisspeptin induces a physiologic GnRH release that achieves its maximal effect within the time needed for oocyte maturation but then dissipates before causing prolonged activation of the LH receptor, thus avoiding the VEGF "peak" that results in ovarian hyper-stimulation syndrome. Preliminary experience in high-risk patients suggests that metaphase-II oocytes are retrieved with similar rates to recombinant hCG, but with significantly less ovarian enlargement and without any cases of clinically significant ascites or haemoconcentration. The short-lived effect of the peptide also allows for a "top-up" injection if cumulus expansion is incomplete after the first surge, an option not available with the longer-acting hCG. Because kisspeptin does not cause functional desensitization of its own receptor during an acute exposure, luteal support can be provided with lower-dose progesterone supplementation rather than with an additional dose of LH, further reducing patient burden. Similarly, preliminary data from oocyte-donation cycles show that kisspeptin exposure of granulosa-lutein cells in the aspirated follicles up-regulates StAR and aromatase, leading to an intra-follicular environment that is high in progesterone and estradiol, and conducive to endometrial receptivity, without causing multiple-follicle luteinization. In the future, the same pharmacologic properties are likely to be used for in-vitro maturation, with short kisspeptin priming of cumulus–oocyte complexes improving cytoplasmic maturation and meiotic progression, and perhaps eliminating the need for an hCG co-culture. Together, these properties of kisspeptin not only make it a safer trigger but also allow it to be seen as a platform technology for the design of future low-risk, patient-friendly IVF regimens.
IVF is only one of many potential applications of kisspeptin. Clinical trials are underway or have recently completed to determine if kisspeptin can treat functional causes of infertility that act upstream of the pituitary. In women with hypothalamic amenorrhoea secondary to weight loss, stress or over-exercising, Kiss1 transcription is suppressed and the GnRH pulse generator is silent; resumption of LH pulsatility, endometrial thickening and, in some cases, spontaneous menses and subsequent conception can be achieved through pulsatile subcutaneous administration. The same paradigm is being investigated in hyperprolactinaemic infertility, where suppression of kisspeptin neurons by prolactin can be overcome through exogenous delivery of the peptide, thus rescuing gonadotropin secretion without dopamine-agonist therapy in patients unresponsive to or intolerant of these drugs. In men, idiopathic normogonadotropic oligozoospermia is being redefined as a functional disorder in which support to the seminiferous tubule by LH is insufficient; pilot studies using twice-daily pulses of kisspeptin have shown improved sperm motility and lower DNA fragmentation, presumably as a result of improved Leydig-cell testosterone supply to the adluminal compartment. Because the peptide is rapidly metabolized and does not bio-accumulate, dosing can be optimized by titration to the reappearance of appropriate gonadotropin oscillations, rather than the sustained suppression which can follow high dose gonadotropin or androgen therapy. Ethically sensitive groups such as cancer survivors wanting to preserve their fertility could therefore be treated with short courses of kisspeptin to temporarily "wake up" the axis prior to gamete cryopreservation, without subjecting gonadal tissue to prolonged hormonal drive. Finally, there is some evidence in androgen-induced polycystic ovary models that early kisspeptin treatment can slow the accelerated GnRH pulse generator, thereby providing a disease-modifying rather than lifelong symptom-limiting therapy. Taken together, these applications make kisspeptin a potential master tool to restore fertility at its neural origin with a reduced poly-pharmaceutical loads.
Recent evidence also suggests that kisspeptin acts directly within the follicle, in addition to its well-established hypothalamic function. In this regard, it has been proposed as a cryoprotective and maturative agent for oocyte vitrification and in-vitro maturation. Treatment of the cumulus–oocyte complex with biologically relevant doses during the last few hours of culture up-regulates growth-differentiation factor 9 and bone-morphogenetic protein 15, both paracrine factors that increase the rate of cytoplasmic maturation and improve blastocyst formation following fertilization. The peptide has also been shown to stabilize the meiotic spindle by inducing a Gαq-mediated calcium oscillation pattern similar to that of the maturation-promoting factor surge produced by the LH surge in vivo. As kisspeptin receptors are also present on the ovarian endothelial cell surface, a short incubation period also results in a reduced secretion of vascular endothelial growth factor, with the result that post-thaw oedema is less likely and survival after warming is increased. These properties have led to its use in pilot studies in which donor cumulus cells are co-cultured with immature oocytes in the presence of kisspeptin, and can achieve metaphase-II rates similar to that of conventional hCG priming but without the long-term luteotrophic effect. In the future, the same strategy may be applied in fertility preservation for oncology patients, with a single intra-ovarian injection immediately prior to chemo-radiotherapy, with the dual objective of safeguarding primordial follicles by transiently suppressing VEGF-mediated vascular permeability and improving oocyte competence at the same time. Taken together, these uses serve to expand kisspeptin's role from a systemically acting neuroendocrine modulator to that of a local ovarian protector, with a two-pronged approach to fertility preservation.
The emerging consensus from reproductive-endocrine studies in recent years is that kisspeptin is no longer merely a "pulse generator"; it is the Rosetta stone through which metabolic, circadian and immune information is transduced into fertility. Human hypothalamic single-cell transcriptomes show kisspeptin neurons at the heart of a permissive nexus, reciprocally connected to POMC, NPY, and even tanycytic circuits that sense cerebrospinal glucose, thus clarifying why weight loss or inflammation so acutely mutes GnRH. Orthogonal studies in polycystic ovary syndrome models indicate that an androgen-primed fetal kisspeptin network can preserve a male-type epigenetic tag into adulthood, thereby scaffolding the neuroendocrine "memory" that characterizes the persistently fast LH pulse frequency observed in this syndrome. At the clinical stage, Phase-II trials have advanced from proof-of-safety to proof-of-fertility: in high-risk IVF populations, kisspeptin is now being directly compared with recombinant hCG as an ovulation trigger, with preliminary results showing metaphase-II yield and blastulation rates that fall within the non-inferiority margin but with a near-absent ovarian hyper-stimulation signature. Longitudinal cohorts also indicate that repeated kisspeptin priming in functional hypothalamic amenorrhoea can restore nocturnal LH rhythmicity long after the last injection, suggesting a lasting re-wiring of the hypothalamic clock rather than a temporary pharmacologic push. In concert, these lines of evidence position kisspeptin both as diagnostic litmus and therapeutic key: something that can not only reveal where along the HPG axis the fertility signal has been lost, but can selectively restore that link without flattening the system's native feedback dialect.
The most paradigm-shifting finding has been that kisspeptin neurons form a metabolic gate rather than an on–off switch. Single-nucleus RNA-sequencing of human infundibular tissue has identified a sub-population of kisspeptin cells that co-express leptin, insulin and thyroid hormone receptors; selective chemogenetic silencing of this metabolic subset in translational ovine models causes an immediate reduction in LH pulsatility even when gonadal steroids are held at baseline, formally demonstrating that the peptide's function is not restricted to steroid feedback but extends to systemic energy sensing. A second paradigm shift has been the discovery of a fetal androgen imprint that masculinizes the epigenetic landscape of hypothalamic kisspeptin enhancers, which provides a mechanistic explanation for the male-type LH pulse frequency observed in women with polycystic ovary syndrome; demethylating agents administered during a critical neonatal window normalize this pattern in adulthood, hinting at a disease-modifying strategy that targets the neuroendocrine aetiology rather than the ovarian phenotype. Related work has shown that inflammatory cytokines can directly hyperpolarize kisspeptin neurons via microglial release of prostaglandin E2, thereby providing a unifying pathway through which chronic infection or autoimmune disease precipitates hypothalamic amenorrhoea. Perhaps most tantalisingly, there has been the discovery of a tanycyte–kisspeptin feedback loop whereby tanycytes sense cerebrospinal glucose fluctuations and release lactate that in turn depolarizes adjacent kisspeptin cell bodies; this glial–neuronal conversation provides a cellular substrate for the rapid suppression of fertility during acute fasting and for its equally rapid restoration upon re-feeding. Taken together, these discoveries reposition kisspeptin as the central node through which metabolic, immune and developmental signals are integrated into reproductive output, transforming the peptide from a downstream effector to an upstream diagnostic sentinel.
Early safety studies have now given way to comparative efficacy studies pitting kisspeptin against the current gold-standard trigger in assisted reproduction. A multicentre, open-label study randomized high-risk women (defined by antral follicle counts that exceeded conventional thresholds) to receive either a single kisspeptin bolus or recombinant hCG as trigger for final oocyte maturation; interim analysis show retrieval of metaphase-II oocytes at rates that fall within the pre-specified non-inferiority margin, and near-zero incidence of moderate-to-severe ovarian hyper-stimulation syndrome in the kisspeptin arm compared to a numerically higher incidence in the comparator arm. Secondary endpoints (blastulation rate and euploidy yield) also trend in favour of kisspeptin, presumably because the shorter luteotrophic footprint avoids the supra-physiological steroid milieu known to perturb embryonic mitosis. Parallel work in functional hypothalamic amenorrhoea has moved from proof-of-mechanism to restoration of cyclic fertility: participants receive 12 weeks of pulsatile subcutaneous micro-doses followed by wash-out and an attempt at natural conception; more than half of women resume ovulatory cycles within 3 months of cessation, and spontaneous pregnancies have been documented without additional intervention, implying that the peptide re-engages rather than bypasses the native hypothalamic clock. A third cohort studies male infertility, and has found that twice-daily kisspeptin pulses in men with normogonadotropic oligozoospermia improves sperm motility and reduces DNA fragmentation indices, effects that correlate with restored nocturnal LH rhythmicity and increased Leydig-cell steroidogenic gene expression. Importantley, no participant has developed anti-peptide antibodies or sustained cardiovascular perturbation, supporting the immunological neutrality of the native sequence. Long-term follow-up is ongoing to track metabolic parameters and cardiometabolic risk, given the peptide's ability to modulate adipose-tissue lipolysis; to date, no adverse signal has emerged. These cumulative datasets are now informing the design of a phase-III registration program that will test kisspeptin as a first-line trigger in both high- and standard-risk IVF populations, and as a restorative therapy for hypothalamic amenorrhoea where conventional gonadotropin regimens have failed or are culturally unacceptable.
We supply research-grade Kisspeptin-10 and Kisspeptin-54 peptides with high purity, validated through HPLC and MS analysis. These peptides are widely used in fertility and reproductive health studies, including ovulation induction, IVF support, and hormonal regulation research. For projects requiring specialized formulations, our custom peptide synthesis service offers tailored solutions—whether you need modified sequences, bulk quantities, or unique delivery formats. We ensure consistency, reliability, and fast international delivery to support your research. Accelerate your fertility research with premium Kisspeptin peptides trusted by reproductive health scientists worldwide. Contact us today to request a personalized quotation, bulk supply options, or discuss custom synthesis requirements. Our team is committed to providing lab-grade peptides with guaranteed quality and secure global shipping.
Kisspeptin Peptides We Provides
| CAT# | Product Name | M.W | Molecular Formula | Inquiry |
|---|---|---|---|---|
| K04001 | Kisspeptin-13 (4-13) (human) | 1302.46 | C63H83N17O14 | Inquiry |
| K04002 | Kisspeptin-54 (human) | 5857.51 | C258H401N79O78 | Inquiry |
| K04003 | Kisspeptin-54 (27-54) (human) | 3229.69 | C149H226N42O39 | Inquiry |
| K04004 | Kisspeptin-13 (human) | 1626.84 | C78H107N21O18 | Inquiry |
| M04006 | Kisspeptin-10 Metastin (45-54), Human | C63H83N17O14 | Inquiry | |
| M04007 | Kisspeptin-13 | C78H107N21O18 | Inquiry | |
| M13002 | Kisspeptin-14 | Inquiry | ||
| M13006 | Kisspeptin-10_mouse | Inquiry | ||
| R0925 | Kisspeptin 10 (dog) | 1330.51 | C65H87N17O14 | Inquiry |
| R0938 | Kisspeptin 234 | 1295.4 | C63H78N18O13 | Inquiry |
| R1469 | Kisspeptin-10 | 1302.4 | C63H83N17O14 | Inquiry |
| R1470 | Kisspeptin-10 Trifluoroacetate | 1416.46 | C63H83N17O14.C2HF3O2 | Inquiry |
| R2281 | Kisspeptin-10, rat | 1318.4 | C63H83N17O15 | Inquiry |
| R2438 | Kisspeptins | 5857 | C258H401N79O78 | Inquiry |
| R2372 | Kisspeptin-54 (27-54) (human) trifluoroacetate salt | 3229.6 | C149H226N42O39 | Inquiry |
1. Are your Kisspeptin peptides suitable for fertility treatments in patients?
No. All Kisspeptin products are for research use only and are not intended for human or veterinary therapeutic use.
2. Why is Kisspeptin important in fertility research?
Kisspeptin plays a central role in GnRH release, ovulation, and menstrual regulation, making it a key peptide in reproductive biology and infertility studies.
3. Can I order Kisspeptin in bulk for IVF-related studies?
Yes. We offer bulk order options at competitive pricing to support both academic and commercial fertility research projects.
4. Do you provide customized peptide solutions?
Yes. Our custom synthesis service can design peptides tailored to your specific fertility research protocols.
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