# Kisspeptin, LH pulses and desensitization

> Keystone Peptides on kisspeptin and hormonal rhythm — Keystone Peptides follows LH pulses and the fading response to repeated kisspeptin exposure in studies of hypothalamic amenorrhea.

**Reproductive signaling**

The initial response looks dramatic. My curiosity shifts to the response that follows it.

## LH pulse frequency

Kisspeptin research has a rhythm running through it. In [a study of kisspeptin-10 in healthy men](https://pubmed.ncbi.nlm.nih.gov/21632807/), administration stimulated LH and increased its pulse frequency. An LH pulse is a rise in the measured hormone over time; following those rises reveals something that a single concentration would miss.

Initially, hormone height seemed the obvious yardstick to me. Pulse frequency makes the question more interesting: how often does the signal arrive? That does not turn the experiment into a prescription. It establishes a response in the men studied, under that research protocol, and gives the later work on suppressed reproductive signaling a useful point of comparison.

## Hypothalamic amenorrhea

In [a study of five women with hypothalamic amenorrhea](https://pubmed.ncbi.nlm.nih.gov/24517142/), kisspeptin-54 infusion restored pulsatile LH secretion. The reported pulse count rose from 1.6 to 5.0 per 8 h versus vehicle, the comparison solution. At the highest infusion rate, however, the response weakened during the infusion.

That is an unusually revealing combination: a response the researchers wanted to restore, and a limitation appearing within the same experiment. I read the restored pulses with real interest. I also resist turning them into a claim about sustained cycle recovery or pregnancy, because this result concerns measured LH pulsatility in the women studied. The question of how a response persists deserves its own experiment.

## The response after repeated exposure

The clearest warning against assuming a steady benefit comes from [the repeated-administration study in women with hypothalamic amenorrhea](https://pubmed.ncbi.nlm.nih.gov/19820030/). The mean LH increment was 24.0 ± 3.5 IU/L within 4 h on day 1; the day-14 response was 2.5 ± 2.2 IU/L. The researchers described tachyphylaxis, the rapid loss of response with repeated exposure.

I distrust an enthusiastic account of reproductive stimulation that omits this comparison. The contrast is already inside the human experiment. An important biological signal can become less effective when repeatedly supplied, and the first response offers an incomplete picture of that behavior.

![Side by side bars show a larger LH response on day 1 than day 14](images/lh-response.svg)

*Women with hypothalamic amenorrhea: the mean LH increment within 4 h on day 1 and the day-14 response, in IU/L, as reported in the [repeated-administration study](https://pubmed.ncbi.nlm.nih.gov/19820030/); whiskers show the reported ± values.*

## Receptor responsiveness

A [review of KISS1R pharmacology](https://pubmed.ncbi.nlm.nih.gov/25765628/) describes desensitization, movement of receptors into the cell and recycling of receptors that have regained responsiveness. Those processes help explain why the pattern of exposure can change the reproductive hormone response.

The architectural comparison fails me at this point. A stone stays put. A living receptor changes its responsiveness. The [IVF experiments](/ivf) interest me partly because they ask a more specific question about an egg-maturation trigger, rather than assuming that continual stimulation would be desirable.

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Keystone Peptides follows my fascination with kisspeptin in published research, an editorial interest with no medical business behind its name and no medical advice in its pages.