Endocrinology 2012-10-01

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.

Erik Hrabovszky, Máté T Sipos, Csilla S Molnár, Philippe Ciofi, Beáta Á Borsay, Péter Gergely, László Herczeg, Stephen R Bloom, Mohammad A Ghatei, Waljit S Dhillo, Zsolt Liposits

Index: Endocrinology 153(10) , 4978-89, (2012)

Full Text: HTML

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.


Related Compounds

  • Neurokinin B trif...

Related Articles:

Current and future applications of GnRH, kisspeptin and neurokinin B analogues.

2013-08-01

[Nat. Rev. Endocrinol. 9(8) , 451-66, (2013)]

Neuroanatomy of the kisspeptin signaling system in mammals: comparative and developmental aspects.

2013-01-01

[Adv. Exp. Med. Biol. 784 , 27-62, (2013)]

Alteration in neonatal nutrition causes perturbations in hypothalamic neural circuits controlling reproductive function.

2012-08-15

[J. Neurosci. 32(33) , 11486-94, (2012)]

Minireview: kisspeptin/neurokinin B/dynorphin (KNDy) cells of the arcuate nucleus: a central node in the control of gonadotropin-releasing hormone secretion.

2010-08-01

[Endocrinology 151(8) , 3479-89, (2010)]

Role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in cutaneous vasodilatation and the estrogen modulation of body temperature.

2012-11-27

[Proc. Natl. Acad. Sci. U. S. A. 109(48) , 19846-51, (2012)]

More Articles...