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Hypothalamic Kisspeptin Neurons: Integral Elements of the GnRH System

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Abstract

Highly sophisticated and synchronized interactions of various cells and hormonal signals are required to make organisms competent for reproduction. GnRH neurons act as a common pathway for multiple cues for the onset of puberty and attaining reproductive function. GnRH is not directly receptive to most of the signals required for the GnRH secretion during the various phases of the ovarian cycle. Kisspeptin neurons of the hypothalamus convey these signals required for the synchronized release of the GnRH. The steroid-sensitive anteroventral periventricular nucleus (AVPV) kisspeptin and arcuate nucleus (ARC) KNDy neurons convey steroid feedback during the reproductive cycle necessary for GnRH surge and pulse, respectively. AVPV region kisspeptin neurons also communicate with nNOS synthesizing neurons and suprachiasmatic nucleus (SCN) neurons to coordinate the process of the ovarian cycle. Neurokinin B (NKB) and dynorphin play roles in the GnRH pulse stimulation and inhibition, respectively. The loss of NKB and kisspeptin function results in the development of neuroendocrine disorders such as hypogonadotropic hypogonadism (HH) and infertility. Ca2+ signaling is essential for GnRH pulse generation, which is propagated through gap junctions between astrocytes-KNDy and KNDy-KNDy neurons. Impaired functioning of KNDy neurons could develop the characteristics associated with polycystic ovarian syndrome (PCOS) in rodents. Kisspeptin-increased synthesis led to excessive secretion of the LH associated with PCOS. This review provides the latest insights and understanding into the role of the KNDy and AVPV/POA kisspeptin neurons in GnRH secretion and PCOS.

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Acknowledgements

Dr. Jyoti Parkash is thankful to the University Grants Commission (UGC) for start-up grant F.30-318/2016 (GP-105) and DST-Science and Engineering Research Board (SERB) for Early Carrier Research Grant ECR/2015/000240 (GP-90), and Core Research Grant CRG/2020/003257 (GP-176). Mr. VP is thankful to SERB, DST, for the Junior and Senior Research Fellowship. TA and RS are also thankful to CSIR for the JRF and SRF in carrying out this research work. Dr. Jyoti Parkash is also thankful to the Central University of Punjab for RSM-CUPB/CC/16/00/13 for providing financial assistance, space, and infrastructure to carry out this research. The authors acknowledge the use of Inkscape 1.2 licensed by a GNU General Public License, version 3, and Servier Medical Art bank (https://smart.servier.com) licensed by a Creative Commons Attribution 3.0 Unported License to create schematic Figs. 1, 2, and 3.

Funding

This work is supported by the DST- Science and Engineering Research Board (SERB), Early Carrier Research grant ECR/2015/000240 (GP-90), Core Research Grant CRG/2020/003257 (GP-176), the University Grants Commission (UGC start-up grant F.30–318/2016 GP-105), and the Central University of Punjab RSM grant- CUPB/CC/16/00/13.

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  1. Department of Zoology, School of Basic Sciences, Central University of Punjab, Ghudda, Bathinda, 151401, Punjab, India

    Vikash Prashar, Tania Arora, Randeep Singh & Jyoti Parkash

  2. Department of Computational Sciences, School of Basic Sciences, Central University of Punjab, Ghudda, Bathinda, 151401, Punjab, India

    Arti Sharma

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  1. Vikash Prashar
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VP drafted and wrote the article. TA and RS reviewed the article, and AS and JP reviewed and approved the article’s final version.

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Prashar, V., Arora, T., Singh, R. et al. Hypothalamic Kisspeptin Neurons: Integral Elements of the GnRH System. Reprod. Sci. 30, 802–822 (2023). https://doi.org/10.1007/s43032-022-01027-5

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