Investigating the KNDy Hypothesis in Humans by Coadministration of Kisspeptin, Neurokinin B, and Naltrexone in Men.
Narayanaswamy. Shakunthala S; Prague. Julia K JK; Jayasena. Channa N CN; Papadopoulou. Deborah A DA; Mizamtsidi. Maria M; Shah. Amar J AJ; Bassett. Paul P; Comninos. Alexander N AN; Abbara. Ali A; Bloom. Stephen R SR; Veldhuis. Johannes D JD; Dhillo. Waljit S WS
Key Findings
- Kisspeptin alone dramatically increased LH levels and LH pulse frequency.
- Neurokinin B by itself had no impact on LH or other gonadotropins.
- Combining neurokinin B with kisspeptin reduced the LH increase, whereas combining naltrexone with kisspeptin boosted LH pulse amplitude.
Practical Outcomes
- For biohackers interested in boosting the reproductive hormone axis, kisspeptin looks promising, and pairing it with an opioid antagonist like naltrexone might enhance the effect. Adding neurokinin B appears unnecessary or even counter‑productive. The findings are based on a very small sample, so any protocol should be tested cautiously and under medical supervision.
Summary
In a tiny study of healthy men, giving the peptide kisspeptin caused a strong rise in the hormone LH, which drives testosterone production. Adding the opioid blocker naltrexone made the LH pulses even bigger, while the other peptide neurokinin B did nothing on its own and actually dampened kisspeptin's effect when combined.
Abstract
A subpopulation of hypothalamic neurons colocalize three neuropeptides, namely kisspeptin, neurokinin B (NKB), and dynorphin, collectively termed KNDy neurons. Animal studies suggest they interact to affect pulsatile GnRH release (KNDy hypothesis); kisspeptin stimulates, NKB modulates, and dynorphin (an opioid) inhibits. To investigate the KNDy hypothesis in humans, we assessed for the first time the effects of the coadministration of kisspeptin-54, NKB, and an opioid receptor antagonist, naltrexone, on LH pulsatility (surrogate marker for GnRH pulsatility) and gonadotropin release. This was an ethically approved prospective, single-blinded, placebo-controlled study. Healthy male volunteers (n = 5/group) attended our research facility for eight study visits. After 1 hour of baseline blood sampling, participants received a different intervention at each visit: oral 50 mg naltrexone, 8-hour iv infusions of vehicle, 2.56 nmol/kg · h NKB, 0.1 nmol/kg · h kissspeptin-54 (KP) alone and in combination. Frequent blood sampling to measure plasma gonadotropins and sex steroids was conducted and LH pulsatility was determined using blinded deconvolution analysis. All kisspeptin and naltrexone containing groups potently increased LH and LH pulsatility (P < .001 vs vehicle). NKB alone did not affect gonadotropins. NKB+KP had significantly lower increases in gonadotropins compared with kisspeptin alone (P < .01). Naltrexone+KP was the only group to significantly increase LH pulse amplitude (P < .001 vs vehicle). Our results suggest significant interactions between the KNDy neuropeptides on LH pulsatility and gonadotropin release in humans. This has important implications for improving our understanding of GnRH pulse generation in humans.
Study Information
pubmed
2016
2016-07-05T00:00:00.000Z
10.1210/jc.2016-1911
33
39