Reproduction poses a substantial burden, especially for mammalian females. Puberty onset serves as a vital checkpoint, regulated based on the body’s energy state, to prevent inappropriate reproductive activity under malnutrition. However, the neural basis of this puberty checkpoint remains poorly understood. Here, we demonstrate that peripubertal malnutrition in female mice reduces the synchronous activity episodes of arcuate kisspeptin neurons, which are critical regulators of the gonadotropin axis. Improved dietary availability increased the frequency of this pulsatile activity, facilitating puberty onset. Using a viral-genetic approach, we show that the activity of agouti-related protein neurons in the arcuate nucleus, a hunger center, can bidirectionally regulate the pulsatile activity of kisspeptin neurons and follicular maturation in the ovaries. Collectively, a neural circuit connecting feeding to reproductive centers modulates the frequency of pulsatile kisspeptin neuron activity based on dietary availability, which sheds light on the neural basis of the puberty checkpoint.
See detail in Dietary Availability Acutely Influences Puberty Onset via Hypothalamic Neural Circuit. Goto T et al. (2024), BioRxiv
Goto, Teppei, Hagihara, Mitsue, Irie, Satsuki, Abe, Takaya, Kiyonari, Hiroshi, Miyamichi, Kazunari, Dietary availability acutely influences puberty onset via a hypothalamic neural circuit, Neuron
Published in Feb. 25, 2025
(Abstract) Reproduction poses a substantial burden, especially for mammalian females. Puberty onset serves as a vital checkpoint, regulated based on the body?s energy state, to prevent inappropriate reproductive activity under malnutrition. However, the neural basis of this puberty checkpoint remains poorly understood. Here, we demonstrate that peripubertal malnutrition in female mice reduces the synchronous activity episodes of arcuate kisspeptin neurons, which are critical regulators of the gonadotropin axis. Improved dietary availability increased the frequency of this pulsatile activity, facilitating puberty onset. Using a viral-genetic approach, we show that the activity of agouti-related protein neurons in the arcuate nucleus, a hunger center, can bidirectionally regulate the pulsatile activity of kisspeptin neurons and follicular maturation in the ovaries. Collectively, a neural circuit connecting feeding to reproductive centers acts as an adjuster of the frequency of pulsatile kisspeptin neuron activity based on dietary availability, contributing to the neural basis of the puberty checkpoint.
Goto, Teppei, Hagihara, Mitsue, Irie, Satsuki, Abe, Takaya, Kiyonari, Hiroshi, Miyamichi, Kazunari (2023/01/01), Dietary Availability Acutely Governs Puberty Onset via Hypothalamic Neural Circuit, bioRxiv, 2023.09.15.558025
Published in 2023/01/01
(Abstract) Reproduction poses a substantial burden, especially for mammalian females. Puberty onset serves as a vital checkpoint, regulated based on the body’s energy state, to prevent inappropriate reproductive activity under malnutrition. However, the neural basis of this puberty checkpoint remains poorly understood. Here, we demonstrate that peripubertal malnutrition in female mice reduces the synchronous activity episodes of arcuate kisspeptin neurons (SEskiss), which are critical regulators of the gonadotropin axis. Improved dietary availability boosts SEskiss frequency, facilitating puberty onset. Using a viral-genetic approach, we show that the activating agouti-related protein neurons in the arcuate nucleus (ARCAgrp neurons), a hunger center, suppresses SEskiss, even with enough food. Conversely, loss-of-function of ARCAgrp neurons enhances SEskiss during malnutrition, partly promoting irregular sexual maturation. Collectively, a neural circuit connecting feeding to reproductive centers is responsible for disinhibiting SEskiss frequency based on dietary availability, which sheds light on the neural basis of puberty checkpoint.HighlightsThe pulsatile activity of arcuate kisspeptin neurons emerges and grows before vaginal opening.Pubertal impairment resulting from malnutrition is associated with a reduction in the pulsatile activity of kisspeptin neurons.Pubertal recovery by food availability follows the elevated pulsatile activity of kisspeptin neurons during catch-up growth.The arcuate Agrp neurons suppress the frequency of pulsatile activity of kisspeptin neurons under negative energy balance.Competing Interest StatementThe authors have declared no competing interest.