Does the KNDy Model for the Control of Gonadotropin-Releasing Hormone Pulses Apply to Monkeys and Humans?
Lehman. Michael N MN; He. Wen W; Coolen. Lique M LM; Levine. Jon E JE; Goodman. Robert L RL
Key Findings
- KNDy neurons (kisspeptin, neurokinin B, dynorphin) act as the GnRH pulse generator in rodents and ruminants.
- Evidence suggests a similar KNDy network exists in primates, but detailed anatomy and function are still unclear.
- Therapeutic drugs that target KNDy peptides are emerging for reproductive disorders, highlighting the need for more human‑specific research.
Practical Outcomes
- For biohackers, the review signals that kisspeptin‑based interventions could eventually modulate reproductive hormone pulses, but current knowledge isn’t enough to design safe, effective protocols. Keep an eye on clinical trials of KNDy‑targeting drugs, and treat any off‑label use of kisspeptin with caution until more human data are available.
Summary
Scientists think a group of brain cells that release kisspeptin, neurokinin B, and dynorphin (called KNDy neurons) helps control the timing of reproductive hormone bursts. This idea is well‑studied in rodents and some farm animals, but we still don’t know exactly how it works in monkeys or people. New drugs that target these KNDy signals are being tested for fertility and other hormone problems, so understanding this system in humans could become important.
Abstract
There is now considerable evidence supporting the role of a subpopulation of neurons in the arcuate nucleus of the hypothalamus that coexpress kisspeptin, neurokinin B, and dynorphin (abbreviated as KNDy neurons) as the long sought-after gonadotropin-releasing hormone (GnRH) pulse generator. The "KNDy hypothesis" of pulse generation has largely been based on findings in rodents and ruminants, and there is considerably less information about the anatomical and functional organization of the KNDy subpopulation in the primate hypothalamus. In this review, we focus on the applicability of this hypothesis, and the roles of kisspeptin, neurokinin B, and dynorphin in reproduction, to humans and nonhuman primates, reviewing available data and pointing out important gaps in our current knowledge. With recent application of drugs that target KNDy peptides and their receptors to therapeutic treatments for reproductive disorders, it is imperative we fully understand the primate KNDy network and its role in the control of GnRH secretion, as well as species differences in this system that may exist between humans, nonhuman primates, and other mammals.
Study Information
pubmed
2019
2019-12-17T00:00:00.000Z
10.1055/s-0039-3400254
27
151