Induced Kisspeptin

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Kisspeptins (including kisspeptin-54 (KP-54), formerly known as metastin) are proteins encoded by the KISS1 gene in humans.

This gene was named KISS1 because of the location of where it was discovered (Hershey, Pennsylvania, home of Hersheyā€™s Kisses).

So it does have something to do with kisses after all! :woozy_face:


Omfg this is surprisingly helping on my menstrual issuesā€¦ with mood / energy.

Note: Take this as a grain of :salt: please. My hormones may be different than you ladies.


Please look into it

@Dreamweaver @SammyG @Dr_Manhattan

Kisspeptin/Kiss1r Signalling and Puberty

  • Kisspeptin/Kiss1r signalling serves as a major trigger for the secretion of GnRH (Gonadotropin-releasing hormone) and gonadotropins.

    • This was first established by de Roux et al. (2003) and Seminara et al. (2003).
  • Kisspeptin plays a crucial role in the onset of puberty.

    • Puberty is initiated by increased pulsatility of GnRH secretion from the hypothalamus.
  • Hypogonadotrophic hypogonadism is a condition characterized by impaired pubertal development and infertility.

    • Occurs when the pulsatility of GnRH is insufficient or absent.
  • Seminara et al. and de Roux et al. first discovered kisspeptinā€™s reproductive significance.

    • They observed families with idiopathic hypogonadotrophic hypogonadism.
    • Seminara and colleagues analyzed the genome of these families and identified a ā€˜L148Sā€™ mutation in the GPR54 gene (Kiss1r) in affected individuals.
  • A mouse model deficient in Kiss1r was created.

    • Mice exhibited the same symptoms of hypogonadotrophic hypogonadism: small testes in males, small ovaries in females, lack of follicular maturation, and delayed vaginal opening.
    • Administration of exogenous GnRH to these mice restored them to a relatively normal phenotype, implying that kisspeptin stimulates GnRH release.
  • Conclusions from these studies:

    • Kiss1r is integral for normal GnRH secretion and for puberty.
    • Kiss1 geneā€™s peptide (kisspeptin) may be the stimulus for GnRH secretion.
  • Mutations in the Kiss1r gene can also lead to precocious puberty, where puberty begins earlier than usual.

    • Initial studies found an autosomal dominant activating mutation in the Kiss1r gene in individuals with precocious puberty.

Effects of Sex Steroids on Kisspeptin Neurons

  • Estrogens have both negative and positive feedback effects on GnRH (Gonadotropin-releasing hormone) secretion.

    • The mechanisms and neuroanatomical pathways for this dual feedback were previously unclear as mammalian GnRH neurons do not express requisite receptors.
  • Post discovery of kisspeptinā€™s reproductive role, the hypothesis arose that feedback effects could be mediated by kisspeptin neurons.

    • This was investigated by studying the expression of Kiss1 mRNA in the ARC (Arcuate nucleus) and RP3V (Rostral periventricular area of the third ventricle) in response to gonadal steroids.
    • Differential regulation was observed in these regions, particularly estradiol stimulation of RP3V kisspeptin neurons and inhibition of ARC kisspeptin neurons.
    • At the time of the preovulatory LH (Luteinizing hormone) surge, Kiss1 mRNA expression increased in the RP3V but decreased in the ARC.
    • Preliminary evidence suggests that kisspeptin neurons in the ARC mediate negative feedback, while those in the RP3V mediate positive feedback.
  • Estrogen, acting through ERĪ± (Estrogen Receptor Ī±), achieves both positive and negative feedback in kisspeptin neuron populations.

    • This might involve classical (for positive) and non-classical (for negative) receptor signaling.
    • Divergent epigenetic regulation of the Kiss1 promoter region between the ARC and AVPV (Anteroventral periventricular nucleus) also seems significant.
    • Estrogen acting through ERĪ± induces histone acetylation of the Kiss1 promoter and enhanced gene expression in the AVPV, but deacetylation in the ARC.
  • Progesterone receptor is crucial for the positive feedback-induced LH surge, particularly its expression on kisspeptin neurons, and androgen receptor may have a modulating role.

  • Even though ERĪ± signaling in RP3V kisspeptin neurons is vital for positive feedback, ERĪ± signaling in ARC kisspeptin neurons is not a complete requirement for negative feedback.

    • In mice with kisspeptin cell-specific deletion of ERĪ±, estradiol treatment resulted in the expected lack of change in Kiss1 mRNA in the ARC, but the negative feedback regulation of LH concentration remained.
    • This suggests the existence of a redundant negative feedback pathway independent of kisspeptin signaling.
  • Positive feedback is more important in females due to it triggering the preovulatory LH surge, which does not occur in males.

    • Females have a much greater number of kisspeptin neurons in the RP3V.
    • The role of kisspeptin in the male RP3V is still unresolved.


Kisspeptin and Testicular Functionā€”Is It Necessary?


  • It acts on KISS1R on hypothalamic GnRH neurons, stimulating gonadotrophins and downstream sex hormones.
  • Disruption to the central KISS1/KISS1R system leads to reproductive disorders.
  • Kisspeptinā€™s peripheral role in tissues such as the testes is less well understood.

Testicular Function

  • Spermatogenesis is a complex process involving the development of male germ cells into mature spermatozoa.
    • Occurs in the recesses of the Sertoli cells located along the seminiferous tubules of the testes.
    • Regulated by several cell types, hormones, genetic and epigenetic factors.
  • Sertoli cells nourish and provide structural support to germ cells, and Leydig cells synthesise steroid hormones essential for spermatogenesis.
  • Testicular functions are dependent on the hypothalamic-pituitary-gonadal (HPG) axis.
    • LH stimulates Leydig cells to synthesize testosterone.
    • FSH stimulates Sertoli cell function and spermatogenesis.
    • Testosterone and Inhibin B have negative feedback effects at the pituitary and hypothalamic levels.
  • Derangements at any of these steps can cause male infertility.

Effects of Kisspeptin on Sperm Function

  • Studies indicate that kisspeptin has a role beyond the brain.
  • In humans, KISS1 and KISS1R are localized in mature spermatozoa, suggesting a role in male fertility.
    • Kisspeptin can trigger an increase in intracellular calcium in spermatozoa and can enhance sperm motility and transient sperm hyperactivation.
    • These effects are blocked by a KISS1R antagonist, indicating a direct role of kisspeptin in human spermatozoa.
    • No effect of kisspeptin on acrosome reaction was observed.
  • In infertile men, those with normal sperm had significantly higher serum kisspeptin levels compared to men with lower sperm count and quality.
  • Median kisspeptin levels were significantly higher in seminal plasma than blood plasma.
    • A positive association was found between total seminal plasma kisspeptin and several sperm parameters.


  • KISS1 and KISS1R are present in the testes and have direct biological effects in the testis.
  • Patterns of testicular expression and physiological autocrine and paracrine characteristics remain inconclusive.
  • Although kisspeptin may act on testicular germ and somatic cells, its direct effect in in vivo systems is unclear.
  • Further understanding of kisspeptinā€™s role in testicular function could provide potential therapeutic targets for treating male fertility disorders.

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