Kisspeptin

Overview | p53 | p63 | ACE-2 | Prokineticin | Kisspeptin | VEGF | Epigenetics | Neuropathy | Studies

At the moment those of us in RxISK know very little about kisspeptin. Our attention has been drawn to it by another person with post-SSRI sexual dysfunction (PSSD), who has also set up a meeting with one research group working on it. As with other target proteins, there are likely lots of groups working on it.

Articles

Here are some pieces about kisspeptin:

Kisspeptin modulates sexual and emotional brain processing in humans

Kisspeptin: Exploring the hormone which can enhance brain activity associated with love and sex

This Science Daily article tells us kisspeptin has come quickly from something few had heard about until recently to being a master peptide – it contains leads to Belgian and German researchers working in this area.

Kisspeptin and Sexual Behaviour

Current Perspectives on Kisspeptin and Behaviour

One of the PSSD researchers has set up a meeting with Waljit Dhillo who is an authority on kisspeptin. We will report on this once the meeting happens.

Ahead of that meeting, another PSSD researcher asked the team who ran the Baylor Epigenetics study whether in the subjects with PFS there was any difference in KISS1 or KISS1R gene expression in their sample, and it appears there was no difference. This was an inspired approach to take and is exactly the kind of initiative that moves things forward.

There seems to be KISS expression in scrotal skin. At present RxISK contributors between us do not know if this means that KISS expression is similarly unaffected throughout the body.

PSSD-UK organized a meeting on September 27 between PSSD-UK, RxISK and Waljit Dhillo’s team at UCL. The research team there have now been briefed on PSSD and plan to think further about whether there are options for them in this area.

Meeting with UCL Kisspeptin Research Team

This meeting happened and led to notes back and forth to Alexander Cominos – one of the team.

I take your point completely about the difficulties in running a study – the money, logistics, and time to set it up.
But before getting to that point, if it makes theoretical sense to try a manipulation of kisspeptin systems in PSSD sufferers, it would be wise to have 1, 2 or 3 volunteers to give you a practical sense of whether this would be worthwhile.  I am thinking about the point that kisspeptin seems if anything to have a dysphoric rather than euphoric effect.  This is rather like ketamine which in lots of ways looked a good bet in PSSD but we tried it in 3 volunteers and it was dysphoric in people who had had a prior SSRI.
Provided kisspeptin is safe and it seems like it is given the studies you’ve done, a 2-3 person test run would not need to go through an ethics committee – there are PSSD sufferers who would not have suicided or gone to Dignitas if offered a chance to do something useful like this.
If exposure to kisspeptin or something that is on the market and is known to modulate kisspeptin systems showed some benefit – it would be much easier for us to raise the funds and easier to get through ethics.
This brings me back to the theoretical angle.  Kisspeptin is clearly fascinating – as is PSSD.  My hunch is PSSD links to broader SSRI withdrawal problems that do not show any sexual dysfunction and the temptation on our side is perhaps to reach for something like kisspeptin because it is so obviously involved in sex – but oestrogen and testosterone at the moment don’t seem to do much for PSSD and the latest research I gather suggests they do have something to do with sex also.  (Although Tamoxifen – for some reason does seem to show some temporary benefits in some).
If anyone in the team has the time to write any notes (a page or two) on possible interfaces between PSSD and kisspeptin – these would be great to get and would help us at the PSSD end track whether we developments we see point to any convergence with kisspeptin – which we can keep you updated about.
Again thanks for meeting and for responding to quickly  – David
David – Many thanks for your reply.

To try anything (even in a single volunteer), requires full ethical approvals here. This is quite an undertaking and takes a few months usually.

As there is no literature on PSSD and kisspeptin as yet, it is difficult to provide a report. I would say that kisspeptin does definitely have some actions through serotonin pathways (at least in rodent work) as well as many other neuroendocrine pathways. So there is a chance that it may have effects where the serotonin system or others is disturbed such as in PSSD. Our recent review can be found here and you can search the document for ‘serotonin’:

https://www.frontiersin.org/articles/10.3389/fendo.2022.928143/full.

We do have data that kisspeptin can improve sexual desire pathways in women (and men) with low sexual desire:

 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2797718.

So, it would indeed be nice to see how KP can affect patients with PSD if we had funding for this. Hopefully one day. —  Alex.

Since this interaction with UCL, Daniel, one of the most active of an increasing army of citizen researchers on PSSD, has uncovered A Fascinating Article on interactions between Kisspeptin and VEGF  (See VEGF). The UCL group have shown that Kisspeptin increases Penile Size. The link to VEGF may show just how this happens – Kisspeptin through VEGF can literally lead to more blood vessels and more blood. This is clearly needed for pregnancy but also for the means of getting pregnant and there is evidence it might also be important in helping small fibre nerve endings to regrow.  They can’t regrow in the absence of a blood supply.

So perhaps if people out there starting spreading the word about Kisspeptin, VEGF and have a bigger Penis and Clitoris, the world might start to take notice and we might get somewhere.

Comments

  1. Here’s a small study from the Medical University of Silesia, which may actually be very important to understanding how SSRIs cause sexual dysfunction. Kisspeptin mRNA expression levels were almost twice as high in the Amygdalas of the rats given escitalopram compared to the control. Meanwhile, levels on kisspeptin in the striatum, cerebellum and brainstem of rats given escitalopram were much lower than the controls.

    Escitalopram as a modulator of proopiomelanocortin, kisspeptin, Kiss1R and MCHR1 gene expressions in the male rat brain

    https://link.springer.com/article/10.1007/s11033-020-05806-8

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  3. This study shows that microinjections of kisspeptin directly into the medial amygdala of male rats dose-dependently stimulates ex-copula erections, an effect blocked by pre-treatment with a kisspeptin receptor antagonist. Also, the study suggests that Kisspeptin’s role in this aspect of sexual behaviour is independent of downstream GnRH, LH or testosterone.

    Kisspeptin in the medial amygdala and sexual behavior in male rats

    https://www.sciencedirect.com/science/article/pii/S0304394016303627?via%3Dihub#

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  4. This study shows that high doses of Kisspeptin can cause testicular damage in male rats. There are other studies that show both SSRIs and Finasteride can cause similar testicular damage. It’s possible that they both do this by temporarily increasing Kisspeptin to dangerously high levels.

    Kisspeptin-54 at high doses acutely induces testicular degeneration in adult male rats via central mechanisms

    https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2008.00061.x

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697701/

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  5. Dear Dr.Healy & Co.,

    This study seems interesting in explaining genital numbness in PSSD/PFS/PRSD and persistent genital arousal in PGAD, in case Kisspeptin is involved. Here is the study: https://doi.org/10.1186%2F1744-8069-7-90

    Study Summary:
    Adult mice were used to assess pain sensitivity after administration of Kisspeptin or p234 (GPR54/KISS1R antagonist) in the right hind paw. A hot plate and formalin test were performed to assess pain sensitivity.
    Immunohistochemistry was also performed to identify GPR54/KISS1R in the plantar surface of the hind paws.

    Results:
    -Peripheral or intrathecal injection of kisspeptin induced hyperalgesia.
    -GPR54 was localized in “sensory fibers that ascend vertically between keratinocytes to reach the stratum corneum of the epidermis”.
    -Kisspeptin injection induced hyperalgesia in the first and second phase of the formalin test.
    -“Intrauterine injection of the GPR54 antagonist, p234, induced robust analgesia in the formalin test, suggesting that endogenous kisspeptin acts extracellularly to activate GPR54 receptors GPR54 during inflammatory pain.”

    Conclusion:
    Modulation of Kisspeptin and its receptor activity may explain the reported sensory symptoms. Analgesia may explain the numbness in PSSD/PFS/PRSD while hyperalgesia may explain the symptoms in PGAD.

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  6. This study from Chungbuk National University in South Korea showed another connection between kisspeptin and VEGF-A. This time it was in liver cancer tumors.

    “Furthermore, KiSS1 increased the angiogenic capacity by upregulation of the vascular endothelial growth factor A (VEGF-A) and CD31.”

    https://pubmed.ncbi.nlm.nih.gov/36572562/

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