Frontiers in Endocrinology (Nov 2022)

Kisspeptin-neuron control of LH pulsatility and ovulation

  • Harvey Stevenson,
  • Samuel Bartram,
  • Mikaela Maria Charalambides,
  • Sruthi Murthy,
  • Theo Petitt,
  • Anjali Pradeep,
  • Owen Vineall,
  • Ikenna Abaraonye,
  • Amelia Lancaster,
  • Kanyada Koysombat,
  • Bijal Patel,
  • Ali Abbara

DOI
https://doi.org/10.3389/fendo.2022.951938
Journal volume & issue
Vol. 13

Abstract

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Feedback from oestradiol (E2) plays a critical role in the regulation of major events in the physiological menstrual cycle including the release of gonadotrophins to stimulate follicular growth, and the mid-cycle luteinising hormone (LH) surge that leads to ovulation. E2 predominantly exerts its action via oestrogen receptor-alpha (ERα), however, as gonadotrophin releasing hormone (GnRH) neurons lack ERα, E2-feedback is posited to be indirectly mediated via upstream neurons. Kisspeptin (KP) is a neuropeptide expressed in hypothalamic KP-neurons that control GnRH secretion and plays a key role in the central mechanism regulating the hypothalamic-pituitary-gonadal (HPG) axis. In the rodent arcuate (ARC) nucleus, KP is co-expressed with Neurokinin B and Dynorphin; and thus, these neurons are termed ‘Kisspeptin-Neurokinin B-Dynorphin’ (KNDy) neurons. ARC KP-neurons function as the ‘GnRH pulse generator’ to regulate GnRH pulsatility, as well as mediating negative feedback from E2. A second KP neuronal population is present in the rostral periventricular area of the third ventricle (RP3V), which includes anteroventral periventricular (AVPV) nucleus and preoptic area neurons. These RP3V KP-neurons mediate positive feedback to induce the mid-cycle luteinising hormone (LH) surge and subsequent ovulation. Here, we describe the role of KP-neurons in these two regions in mediating this differential feedback from oestrogens. We conclude by considering reproductive diseases for which exploitation of these mechanisms could yield future therapies.

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