Kisspeptin news and clinical trials

Researchers studied male and female lambs and found that undernutrition increased AgRP neuron input to arcuate kisspeptin neurons. This mechanism likely relays negative energy status to the reproductive axis to inhibit GnRH/LH secretion.

Researchers treated H9c2 cardiomyocytes with 50 or 100 nM Kisspeptin-10 and found it alleviated injury induced by oxygen-glucose deprivation/reperfusion. The study indicates this occurred by enhancing autophagy through the YY1/TFEB axis.

Researchers found that knocking down Slc32a1 in female mice caused earlier vaginal opening and upregulated puberty-related genes including Kiss-1. The findings suggest SLC32A1 regulates puberty onset by modulating GnRH neuron function via GABA-GABA B receptor signaling.

Researchers studied AVPV kisspeptin neurons in mice and found that GnRH neuron responsiveness to kisspeptin activation relies on both the hormone environment and synaptic connectivity. The study also determined that neuromodulatory transmission can occur without fast-synaptic co-transmission.

Researchers found that a subset of SCN neurons releases GABA to potently suppress firing in RP3V kisspeptin neurons in female mice. These findings reveal that this specific circadian neuronal population provides a direct inhibitory input to the kisspeptin network.

New paper in Reproductive sciences (Thousand Oaks, Calif.): Kisspeptin-10 Alleviates Obesity-induced Testicular Oxidative Stress and Mitochondrial Dysfunction via Modulation of Mitophagy and Autophagy Signaling.

A comparative study of kisspeptin isoforms in mice identified KP-13 as the most favorable metabolic regulator. KP-13 improved beta-cell proliferation and protected against apoptosis while avoiding the glucose-elevating effects seen with KP-10 and KP-14.

A study in ovariectomized heifers found that high-frequency administration of kisspeptin or GnRH effectively increased LH pulses but failed to enhance the GnRH-induced LH surge. Results also showed that the LH surge was significantly lower in Brahman heifers compared to Hereford heifers.

A study in rats showed that maternal Kisspeptin-10 treatment partially rescues fetal and postnatal cardiac development disrupted by maternal hypothyroidism. It restored cardiomyocyte proliferation and nuclear density while modulating apoptotic and angiogenic pathways.

A computational study indicates that Kisspeptin-10 binds with significantly higher selectivity to the KISS1R receptor than to dopamine or serotonin receptors. This suggests that the peptide's reported effects on impulsive behaviors likely stem from canonical kisspeptin signaling.

Researchers developed a photoswitchable peptide called azo-senktide to control hypothalamic neurons in female mice. The study found that light activation of this peptide in the arcuate nucleus triggered a luteinizing hormone pulse, revealing dynamics in neurokinin B signaling.

Researchers investigating temporal lobe epilepsy in a rat model found that chronic neuroinflammation disrupts the kisspeptin signalling system. Administration of kisspeptin-10 attenuated neuroinflammation, improved memory discrimination, and increased survival rates in the rats.

A study in a 6-hydroxydopamine-induced rat model of Parkinson's disease found that chronic nasal administration of kisspeptin-54 improved motor and cognitive deficits. Treatment also reduced alpha-synuclein accumulation and restored hippocampal synaptic plasticity.

Researchers found that Dlk1-deficient mice reach puberty at the same age as controls despite lower body weight and reduced hypothalamic kisspeptin expression. This suggests that peripheral sources of Dlk1 contribute to the metabolic and endocrine regulation of pubertal timing.

Researchers measuring follicular fluid in 90 women found that concentrations of Kisspeptin-1, Kisspeptin-54, and VEGF were significantly elevated in patients with PCOS and OHSS. These findings suggest that these markers reflect the biological features of ovarian hyperresponsiveness.

Stephanie B. Seminara posted results for a phase 2 study of 18 participants investigating the use of exogenous kisspeptin 112-121 in treating hypogonadotropic hypogonadism. The study is completed.

New paper in Clinical endocrinology: Seminal Plasma Kisspeptin-1 and Kisspeptin-54 Levels Are Associated With Semen Parameters and Oxidative Stress in Male Infertility.

Researchers demonstrated that stigmasterol treatment delayed puberty and ameliorated reproductive abnormalities in a rat model of central precocious puberty. It achieved this by targeting the IGF-1/PI3K/Akt/mTOR pathway and modulating the Kisspeptin/GnRH axis.

Researchers examining male Syrian hamsters found that Kiss1 mRNA expression and protein levels exhibit significant diurnal variation under long photoperiods. Pinealectomy disrupted these rhythms, highlighting the role of melatonin in synchronizing daily reproductive rhythms.

Researchers conducting a study on 15 healthy men found that daily 8-hour subcutaneous infusions of kisspeptin-10 over 12 days sustained increases in gonadotropin and testosterone secretion. This suggests a potential protocol for treating reproductive disorders.

A study published in Anticancer Research found that kisspeptin signaling suppresses HRAS G12V-induced tumor growth and metastasis in NIH3T3 cells. This suppression occurs by inhibiting SP1-dependent transcription of N-cadherin.

Researchers investigating renal ischemia-reperfusion injury in rats found that naringenin confers renoprotection. Treatment, particularly at reperfusion, restores kisspeptin expression while reducing oxidative stress and tissue damage.

This article provides an overview of the current scientific understanding of kisspeptin, published in the journal Trends in Endocrinology and Metabolism.

This erratum corrects a previously published article regarding IGF-1 supplementation and its impact on oocyte maturation, specifically noting the role of kisspeptin signaling.

Researchers studied 40 girls to determine if kisspeptin and DLK1 levels could distinguish central precocious puberty from premature thelarche. They found that while baseline levels were similar, the percentage change in these peptides post-GnRH stimulation differed significantly between groups.

Researchers found that Kisspeptin-54 protects against sepsis-induced acute lung injury in mice. The study showed it improves survival and reduces inflammation by activating AMPK to suppress the NLRP3 inflammasome.

A study comparing kisspeptin agonists in HEK293 cells found that the C6 analog produced the most sustained intracellular Ca2+ mobilization and the strongest transcriptional response. This prolonged signaling was linked to more pronounced tachyphylaxis compared to hKp10 and hKp54.

New paper in Clinica chimica acta; international journal of clinical chemistry: Kisspeptin-10/basal LH ratio improves differentiation of central precocious puberty and premature thelarche.

Researchers injecting pejerrey fish with homologous Kiss2 found that it induced sperm release and increased androgen levels. The study demonstrated that Kiss2 could directly modulate testicular function, suggesting a local intragonadal role for the peptide.

Researchers investigating premature ovarian insufficiency in rats found that acupuncture at specific points improved ovarian function and modulated the kisspeptin/GPR54 pathway. Compared to an untreated model group, acupuncture restored estrous cycles and altered hormone levels.

A review of six studies indicates that maternal serum kisspeptin levels and placental KISS1/KISS1R expression are often reduced in cases of early pregnancy loss. The findings suggest kisspeptin has potential as a precision biomarker for monitoring early pregnancy viability.

Stephanie B. Seminara, MD terminated a Phase 1 clinical trial of kisspeptin 112-121 and GnRH because the study team lost access to GnRH. The trial, which had 16 participants, was initially designed to assess hormone stimulation testing.

Stephanie B. Seminara, MD posted results for a terminated Phase 1 study that investigated kisspeptin 112-121 and GnRH stimulation in 16 participants. The trial was stopped because the research team no longer had access to GnRH.

Stephanie B. Seminara registered a phase 2 trial to assess whether subcutaneous administration of kisspeptin 112-121 over two weeks can stimulate reproductive hormone release and egg production in 20 women with hypothalamic amenorrhea.

Stephanie B. Seminara registered a Phase 1 trial recruiting 40 participants to use a bolus of Kisspeptin 112-121 to quantify GnRH neuronal function in individuals with and without post-COVID-19 syndrome.