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Review
. 2020;110(3-4):172-184.
doi: 10.1159/000503006. Epub 2019 Aug 30.

Differential Roles of Hypothalamic AVPV and Arcuate Kisspeptin Neurons in Estradiol Feedback Regulation of Female Reproduction

Affiliations
Review

Differential Roles of Hypothalamic AVPV and Arcuate Kisspeptin Neurons in Estradiol Feedback Regulation of Female Reproduction

Luhong Wang et al. Neuroendocrinology. 2020.

Abstract

Mammalian reproductive function includes puberty onset and completion, reproductive cyclicity, steroidogenesis, gametogenesis, fertilization, pregnancy, and lactation; all are indispensable to perpetuate species. Reproductive cycles are critical for providing the hormonal milieu needed for follicular development and maturation of eggs, but cycles, in and of themselves, do not guarantee ovulation will occur. Here, we review the roles in female reproductive neuroendocrine function of two hypothalamic populations that produce the neuropeptide kisspeptin, demonstrating distinct roles in maintaining cycles and ovulation.

Keywords: Anteroventral periventricular nucleus; Arcuate; CRISPR; Estradiol; Kisspeptin; Ovulation; Reproduction.

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Figures

Figure 1.
Figure 1.
Estradiol regulation of firing rate and EPSC frequency in arcuate and AVPV kisspeptin neurons of the hypothalamus. A, Firing rate of arcuate kisspeptin neurons is elevated in cells from KERKO compared to control mice. B, Firing rate is not different between cells from Arc-AAV-Esr1 and Arc-AAV-lacZ OVX+E mice. C, Spontaneous glutamatergic EPSC frequency is regulated by cycle stage (left) and estradiol (right) in arcuate kisspeptin neurons. E, estrus, K, KERKO. D, Knockdown of ERα targeted to the arcuate increases glutamatergic inputs to arcuate KNDy neurons. E, Firing rate of AVPV kisspeptin neurons is elevated during proestrus (left) and by estradiol (right). F, The firing rate decreases in cells from KERKO compared to control and is no longer estradiol-sensitive. G, Spontaneous glutamatergic EPSC frequency is regulated by cycle stage (left) and estradiol (right) in AVPV kisspeptin neurons. *, p<0.05; adapted from [112,119,137] with permission.
Figure 2.
Figure 2.
Distinct roles of arcuate and AVPV kisspeptin neurons in regulating estradiol feedback and reproductive function. A, Knockdown of ERα in arcuate kisspeptin neurons did not alter LH-pulse frequency on estrus (left) but desensitized the LH response to kisspeptin and GnRH challenge. B, Knockdown of ERα in AVPV kisspeptin neurons blunted the proestrous (left) and estradiol-induced (right) surges. C and D, Knockdown of ERα in arcuate (C) but not AVPV (D) kisspeptin neurons alter reproductive cyclicity. Adapted from [119].
Figure 3.
Figure 3.
Schematic diagram of estradiol feedback regulation on ERα in AVPV and arcuate kisspeptin neurons in adulthood. Knockdown of ERα in AVPV kisspeptin neurons blunted LH surge but did not alter reproductive cyclicity whereas knockdown of ERα in arcuate kisspeptin neurons disrupted the cyclicity. From [119].

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