KNDy neuron

KNDy neuron
Details
System Reproductive system
Location Hypothalamus
Anatomical terms of microanatomy

KNDy neurons are neurons in the hypothalamus of the brain that are central to the hormonal control of reproduction. KNDy neurons in the hypothalamus coexpress kisspeptin, neurokinin B (NKB) and dynorphin. They are involved in the negative feedback of Gondaotrophin-releasing hormone (GnRH) release in the Hypothalamic-Pituitary-Gonadal (HPG) axis. Sex steroids released from the gonads act on KNDy neurons as inhibitors of kisspeptin release. This inhibition provides negative feedback control on the HPG axis.

KNDy peptide colocalization was first discovered in 2007 in sheep. It was later confirmed to be present in mice, rats, cows and nonhuman primates. KNDy neurons are thought to be located in the hypothalamus region of human brains due to conservation across most mammalian species.

Other roles of KNDy neurons include influences on prolactin production; puberty; stress' effects on reproduction; and the control of thermoregulation.[1]

GnRH pulse regulation

KNDy neurons control GnRH pulse generation by through release of three known peptides: neurokinin B (NKB), dynorphin and kisspeptin.[1] NKB and dynorphin are the two peptides that regulate the secretion of kisspeptin.[1] NKB is the stimulating peptide which initiates the pulsatile release of GnRH by activating NKB receptors, called TACR3, on mutually connected KNDy neurons to release kisspeptin in an autocrine signalling pathway.[1] Kisspeptin then activates the GPR54 receptors on GnRH neurons inducing the pulsatile release of GnRH and on KNDy neurons, adding to the stimulatory effect of NKB.[2] Eventually the pulse is terminated by dynorphin which acts on κ-opioid receptors (KOR) in KNDy neurons to inhibit NKB and kisspeptin secretion and inhibits GnRH secretion acting directly on GnRH neuron receptors.[2]

Sexual Dimorphism in KNDy neuron Populations

KNDy neurons are most densely located in the arcuate nucleus (ARC) of the hypothalamus, but also exist in the rostral periventricular area of third ventricle (RP3V) and the preoptic area (POA).[1] Expression of the KNDy peptides highlighted has been shown to differentiate between species, sexes and with fluctuating steroidal hormonal levels. Improvements in immunohistochemistry and deep-brain imaging techniques have enabled us to also gain greater information about KNDy cell populations using 3D imagery and it has shown there are also sexual dimorphism in the populations of KNDy.[1] Greater numbers of KNDy neurons have been found in the female ARC, than the male ARC. The RP3V is composed of the anteroventral periventricular nucleus (APVN) and the preoptic periventricular nucleus, where KNDy neurons have been shown to be sexually dimorphic.[3] KNDy populations and sexual dimorphism within them have been found within most species studied, including humans, but presence in the RP3V is primarily associated with research done in rodents, and again more KNDy population have been found here in female rodents than male rodents.[3]

Positive and Negative Steroid Hormone Feedback

The negative feedback of steroid hormones in both males and females is exhibited to control the pulsatile nature of GnRH secretion, subsequently increasing or decreasing the release of LH and FSH from the anterior pituitary.[1] This is mediated by estrogen receptor α (ERα) expressed on KNDy neurons. The binding of estrogen or testosterone to this receptor in the ARC region inhibits KNDy neurons and therefore prevents GnRH release. However, KNDy neurons are also involved in the positive feedback of the HPG axis. This mechanism is best exemplified by the LH surge in the female reproductive cycle, where the increase of estrogen from the growing ovarian follicle causes positive feedback in the AVPV region, and subsequently a rise in LH from the pituitary.[4]

References

  1. 1 2 3 4 5 6 7 Moore, Aleisha M; Coolen, Lique M; Porter, Danielle T; Goodman, Robert L; Lehman, Michael N (2018-07-11). "KNDy Cells Revisited". Endocrinology. 159 (9): 3219–3234. doi:10.1210/en.2018-00389. ISSN 1945-7170. PMC 6098225. PMID 30010844.
  2. 1 2 Hu, Guangfu; Lin, Chengyuan; He, Mulan; Wong, Anderson O.L. (2014-11-01). "Neurokinin B and reproductive functions: "KNDy neuron" model in mammals and the emerging story in fish". General and Comparative Endocrinology. 208: 94–108. doi:10.1016/j.ygcen.2014.08.009. ISSN 0016-6480. PMID 25172151.
  3. 1 2 Hrabovszky, Erik (2014). "Neuroanatomy of the Human Hypothalamic Kisspeptin System". Neuroendocrinology. 99 (1): 33–48. doi:10.1159/000356903. ISSN 1423-0194. PMID 24401651.
  4. Tng, Eng Loon (December 2015). "Kisspeptin signalling and its roles in humans". Singapore Medical Journal. 56 (12): 649–656. doi:10.11622/smedj.2015183. ISSN 0037-5675. PMC 4678402. PMID 26702158.
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