Low degree of overlap between kisspeptin, neurokinin B, and dynorphin immunoreactivities in the infundibular nucleus of young male human subjects challenges the KNDy neuron concept.
Hrabovszky. Erik E; Sipos. Máté T MT; Molnár. Csilla S CS; Ciofi. Philippe P; Borsay. Beáta Á BÁ; Gergely. Péter P; Herczeg. László L; Bloom. Stephen R SR; Ghatei. Mohammad A MA; Dhillo. Waljit S WS; Liposits. Zsolt Z
Key Findings
- Neurokinin B cells and fibers are about five times more abundant than kisspeptin in the human infundibular nucleus.
- Only ~33% of neurokinin B cells also contain kisspeptin, while ~75% of kisspeptin cells also have neurokinin B, showing limited overlap.
- Dynorphin‑producing cells are very rare and their fibers are mostly distinct from kisspeptin fibers.
Practical Outcomes
- If you’re thinking about using kisspeptin‑10 to influence fertility or hormone rhythms, this study warns that human brain chemistry differs from animal models. Expect that kisspeptin alone may have limited impact on GnRH pulse generation in young men, and more human‑focused research is needed before designing protocols.
Summary
In young men, the brain cells that make kisspeptin, neurokinin B, and dynorphin are mostly separate, unlike what’s seen in animals. This means the popular “KNDy neuron” idea doesn’t fully apply to humans, so animal‑based tricks for tweaking hormone pulses may not work the same way in people.
Abstract
Previous immunohistochemical and in situ hybridization studies of sheep, goats, and rodents indicated that kisspeptin (KP), neurokinin B (NKB), and dynorphin A (DYN) are extensively colocalized in the hypothalamic arcuate nucleus, thus providing a basis for the KP/NKB/DYN (KNDy) neuron concept; in both sexes, KNDy neuropeptides have been implicated in the generation of GnRH neurosecretory pulses and in the negative feedback effects of sexual steroids to the reproductive axis. To test the validity and limitations of the KNDy neuron concept in the human, we carried out the comparative immunohistochemical analysis of the three neuropeptides in the infundibular nucleus (Inf; also known as arcuate nucleus) and stalk of young male human individuals (<37 yr). Results of quantitative immunohistochemical experiments established that the regional densities of NKB immunoreactive (IR) perikarya and fibers, and the incidence of afferent contacts they formed onto GnRH neurons, were about 5 times as high as those of the KP-IR elements. Dual-immunofluorescent studies confirmed that considerable subsets of the NKB-IR and KP-IR cell bodies and fibers are separate, and only about 33% of NKB-IR perikarya and 75% of KP-IR perikarya were dual labeled. Furthermore, very few DYN-IR cell bodies could be visualized in the Inf. DYN-IR fibers were also rare and, with few exceptions, distinct from the KP-IR fibers. The abundance and colocalization patterns of the three immunoreactivities showed similar trends in the infundibular stalk around portal blood vessels. Together these results indicate that most NKB neurons in the Inf do not synthesize detectable amounts of KP and DYN in young male human individuals. These data call for a critical use of the KNDy neuron terminology when referring to the putative pulse generator system of the mediobasal hypothalamus. We conclude that the functional importance of these three neuropeptides in reproductive regulation considerably varies among species, between sexes, and at different ages.
Study Information
pubmed
2012
2012-08-17T00:00:00.000Z
10.1210/en.2012-1545