ISSN 1662-4009 (Online)

ESPE Yearbook of Paediatric Endocrinology (2019) 16 1.7 | DOI: 10.1530/ey.16.1.7

Genetic dissection of the different roles of hypothalamic kisspeptin neurons in regulating female reproduction

Wang L, Vanacker C, Burger LL, Barnes T, Shah YM, Myers MG & Moenter SM

Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA

To read the full abstract: Elife 2019;8:e43999.

Two populations of Kisspeptin neurons are described in the hypothalamus. One population is located in the rostral part of the hypothalamus (the anteroventral periventricular nucleus, AVPV); the other is in the arcuate nucleus (ARC). The major difference between these populations is the opposing effects of 17b-estradiol (E2) on Kiss1 expression. E2 increases Kiss1 expression in the AVPV, but inhibits Kiss1 expression in the ARC. In this paper, the authors used a specific and temporally-controlled method to invalidate the estradiol receptor in Kisspeptin neurons. They show that E2 regulates LH surge generation through AVPV kisspeptin neurons, and maintains cyclicity through ARC kisspeptin neurons. This paper is interesting for two main reasons:

1) It describes an innovative CRISPR-Cas9 technique to investigate the role of E2 in different kisspeptin neurons. The hypothalamus is a complex region of the brain with many nuclei which interact with each other. These nuclei are defined by their anatomical location but also by their specific neuroendocrine functions. The specific deletion of one gene in specific hypothalamic population is therefore highly challenging and this technique may be used to investigate neuroendocrine functions at other specific regions.

2) It shows different reproductive cycle contributions of AVPV and ARC kisspeptin neurons. Surprisingly, specific deletion of ERα in ARC kisspeptin neurons did not change LH pulse frequency whereas these neurons are established as the GnRH-pulse generator (see paper 1.8). Additional experiments are needed to explain this unexpected result.

Reference: 1. Han SY, Kane G, Cheong I, Herbison AE Characterization of GnRH Pulse Generator Activity in Male Mice Using GCaMP Fiber Photometry. Endocrinology. 2019;160(3):557–567.

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