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NEUROENDOCRINOLOGY

Origins of the ‘KNDy hypothesis’ of GnRH pulse generation

Nature Reviews Endocrinology volume 18, page 521 (2022)Cite this article

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A major advance in neuroendocrinology in the past 20 years was the discovery that kisspeptin neurons of the arcuate nucleus (ARC), termed KNDy neurons because of their co-expression of kisspeptin, neurokinin B (NKB) and dynorphin, are key oscillators driving pulsatile release of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH). The ARC had been implicated in pulsatile LH secretion since the 1970s, but the specific neurons involved remained a mystery. Co-expression of the three KNDy peptides, first demonstrated in 2007, provided a key clue, but the role of KNDy neurons in pulse generation has its roots in earlier work and, in fact, starts at the end of the acronym ‘KNDy’ with ‘Dy’, which signifies dynorphin, an endogenous opioid peptide (EOP).

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References

Original article

  • Goodman, R. L. et al. Endogenous opioid peptides control the amplitude and shape of gonadotropin-releasing hormone pulses in the ewe. Endocrinology 136, 2412–2420 (1995)

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Related articles

  • Goodman, R. L. et al. Kisspeptin neurons in the arcuate nucleus of the ewe express both dynorphin A and neurokinin B. Endocrinology 148, 5752–5760 (2007)

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  • Lehman, M. N., Coolen, L. M. & Goodman, R. L. Minireview: kisspeptin/neurokinin B/dynorphin (KNDy) cells of the arcuate nucleus: a central node in the control of gonadotropin-releasing hormone secretion. Endocrinology 151, 3479–3489 (2010)

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  • Moore, A. M., Coolen, L. M. & Lehman, M. N. In vivo imaging of the GnRH pulse generator reveals a temporal order of neuronal activation and synchronization during each pulse. Proc. Natl. Acad. Sci. USA 119, e2117767119 (2022)

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Authors and Affiliations

  1. Brain Health Research Institute, Kent State University, Kent, OH, USA

    Michael N. Lehman

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  1. Michael N. Lehman
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Correspondence to Michael N. Lehman.

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The author declares no competing interests.

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Lehman, M.N. Origins of the ‘KNDy hypothesis’ of GnRH pulse generation. Nat Rev Endocrinol 18, 521 (2022). https://doi.org/10.1038/s41574-022-00703-5

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  • DOI: https://doi.org/10.1038/s41574-022-00703-5

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