Developmental sex differences in the peri-pubertal pattern of hypothalamic reproductive gene expression, including Kiss1 and Tac2, may contribute to sex differences in puberty onset.
Developmental sex differences in the peri-pubertal pattern of hypothalamic reproductive gene expression, including Kiss1 and Tac2, may contribute to sex differences in puberty onset.
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下丘脑生殖基因表达（包括Kiss 1和Tac 2）的青春期周围模式的发育性别差异可能导致青春期开始的性别差异。
DOI：
10.1016/j.mce.2022.111654
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发表时间：
2022-07-01
影响因子：
4.1
通讯作者：
Kauffman, Alexander S.
中科院分区：
文献类型：
--
作者：
Semaan, Sheila J.;Kauffman, Alexander S.
关键词：
调节青春期的机制仍然难以捉摸，青春期开始的性别差异（女孩早于男孩）和青春期障碍的根本原因也是如此。神经内分泌青春期的开始以脉动 GnRH 分泌增加为标志，但人们对各种上游生殖神经回路如何以及何时发生发育变化以控制这一过程的了解还很少。我们之前报道过雌性小鼠下丘脑基因表达在青春期前后逐日增加（Kiss1、Tac2）或减少（Rfrp），在外部青春期标志物之前有一些大脑 mRNA 变化。然而，此前并未报道过男性类似的青春期测量结果。在这里，为了确定青春期开始时性别差异背后可能存在的神经性别差异，我们分析了青春期男性并直接将其与同窝雌性进行比较。雄性小鼠的 Kiss1 表达在青春期前后在 AVPV 和 ARC 核中均有所增加，但在几个年龄段的水平低于雌性小鼠。同样，男性 ARC 中的 Tac2 表达在青少年和老年围青春期阶段有所增加，但在大多数年龄段的水平低于女性。相比之下，男性在青少年期和围青春期阶段的 DMN Rfrp 表达和 Rfrp 神经元激活均显着下降，但与女性水平相似。 GnRH 神经元中的 ARC KNDy 神经元激活和 Kiss1r 表达在男性和女性之间均没有差异，也不随年龄而变化。这些发现描绘了发育中男性神经群在青春期前后的一些变化，其中 Kisspeptin 和 NKB 神经元发育模式存在显着的性别差异。这些青春期前后下丘脑的性别差异是否是青春期开始时性别差异的基础，值得进一步研究。
The mechanisms regulating puberty still remain elusive, as do the underlying causes for sex differences in puberty onset (girls before boys) and pubertal disorders. Neuroendocrine puberty onset is signified by increased pulsatile GnRH secretion, yet how and when various upstream reproductive neural circuits change developmentally to govern this process is poorly understood. We previously reported day-by-day peri-pubertal increases (Kiss1, Tac2) or decreases (Rfrp) in hypothalamic gene expression of female mice, with several brain mRNA changes preceding external pubertal markers. However, similar pubertal measures in males were not previously reported. Here, to identify possible neural sex differences underlying sex differences in puberty onset, we analyzed peri-pubertal males and directly compared them with female littermates. Kiss1 expression in male mice increased over the peri-pubertal period in both the AVPV and ARC nuclei but with lower levels than in females at several ages. Likewise, Tac2 expression in the male ARC increased between juvenile and older peri-pubertal stages but with levels lower than females at most ages. By contrast, both DMN Rfrp expressionand Rfrp neuronal activation strongly decreased in males between juvenile and peri-pubertal stages, but with similar levels as females. Neither ARC KNDy neuronal activation nor Kiss1r expression in GnRH neurons differed between males and females or changed with age. These findings delineate several peri-pubertal changes in neural populations in developing males, with notable sex differences in kisspeptin and NKB neuron developmental patterns. Whether these peri-pubertal hypothalamic sex differences underlie sex differences in puberty onset deserves future investigation.
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影响因子：
4.1
作者：
Castellano, J. M.;Navarro, V. M.;Tena-Sempere, M.
通讯作者：
Tena-Sempere, M.
DOI：
10.1073/pnas.1834399100
发表时间：
2003-09-16
影响因子：
11.1
作者：
de Roux, N;Genin, E;Milgrom, E
通讯作者：
Milgrom, E
影响因子：
3.6
作者：
Dror, Tal;Franks, Jennifer;Kauffman, Alexander S.
通讯作者：
Kauffman, Alexander S.
影响因子：
4.1
作者：
CHOWEN, JA;ARGENTE, J;STEINER, RA
通讯作者：
STEINER, RA
影响因子：
4.8
作者：
Guerriero, Kathryn A.;Keen, Kim L.;Terasawa, Ei
通讯作者：
Terasawa, Ei