Kisspeptin Neurons and Estrogen–Estrogen Receptor α Signaling: Unraveling the Mystery of Steroid Feedback System Regulating Mammalian Reproduction

Estrogen produced by ovarian follicles plays a key role in the central mechanisms controlling reproduction via regulation of gonadotropin-releasing hormone (GnRH) release by its negative and positive feedback actions in female mammals. It has been well accepted that estrogen receptor α (ERα) mediate...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-09, Vol.22 (17), p.9229
Main Authors: Uenoyama, Yoshihisa, Inoue, Naoko, Nakamura, Sho, Tsukamura, Hiroko
Format: Article
Language:English
Subjects:
Arcuate nucleus
dynorphin A
Epigenetics
estradiol
Estrogen receptors
Estrogens
Feedback
follicle-stimulating hormone
Follicles
follicular development
Folliculogenesis
Gene expression
Gonadotropin-releasing hormone
Gonadotropins
Hypothalamus
Kiss1 protein
Luteinizing hormone
Mammals
Negative feedback
Neurons
Ovaries
Ovulation
Periventricular nucleus
Physiology
Pituitary (anterior)
Positive feedback
Review
Rodents
Sensory neurons
Sheep
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Summary:Estrogen produced by ovarian follicles plays a key role in the central mechanisms controlling reproduction via regulation of gonadotropin-releasing hormone (GnRH) release by its negative and positive feedback actions in female mammals. It has been well accepted that estrogen receptor α (ERα) mediates both estrogen feedback actions, but precise targets had remained as a mystery for decades. Ever since the discovery of kisspeptin neurons as afferent ERα-expressing neurons to govern GnRH neurons, the mechanisms mediating estrogen feedback are gradually being unraveled. The present article overviews the role of kisspeptin neurons in the arcuate nucleus (ARC), which are considered to drive pulsatile GnRH/gonadotropin release and folliculogenesis, in mediating the estrogen negative feedback action, and the role of kisspeptin neurons located in the anteroventral periventricular nucleus-periventricular nucleus (AVPV-PeN), which are thought to drive GnRH/luteinizing hormone (LH) surge and consequent ovulation, in mediating the estrogen positive feedback action. This implication has been confirmed by the studies showing that estrogen-bound ERα down- and up-regulates kisspeptin gene (Kiss1) expression in the ARC and AVPV-PeN kisspeptin neurons, respectively. The article also provides the molecular and epigenetic mechanisms regulating Kiss1 expression in kisspeptin neurons by estrogen. Further, afferent ERα-expressing neurons that may regulate kisspeptin release are discussed.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22179229