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条件性 Oprk1 依赖的 Kiss1 神经元缺失导致雌性大鼠雌激素依赖性 LH 脉冲中断和 LH 峰减弱。

Conditional Oprk1-dependent Kiss1 deletion in kisspeptin neurons caused estrogen-dependent LH pulse disruption and LH surge attenuation in female rats.

机构信息

Laboratory of Animal Reproduction, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, Aichi, 464-8601, Japan.

Section of Mammalian Transgenesis, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, 444-8787, Japan.

出版信息

Sci Rep. 2023 Nov 22;13(1):20495. doi: 10.1038/s41598-023-47222-5.

DOI:10.1038/s41598-023-47222-5
PMID:37993510
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10665460/
Abstract

The gonadotropin-releasing hormone (GnRH) pulse and surge are considered to be generated by arcuate kisspeptin/neurokinin B/dynorphin A (KNDy) neurons and anteroventral periventricular nucleus (AVPV) kisspeptin neurons, respectively, in female rodents. The majority of KNDy and AVPV kisspeptin neurons express κ-opioid receptors (KORs, encoded by Oprk1) in female rodents. Thus, this study aimed to investigate the effect of a conditional Oprk1-dependent Kiss1 deletion in kisspeptin neurons on the luteinizing hormone (LH) pulse/surge and fertility using Kiss1-floxed/Oprk1-Cre rats, in which Kiss1 was deleted in cells expressing or once expressed the Oprk1/Cre. The Kiss1-floxed/Oprk1-Cre female rats, with Kiss1 deleted in a majority of KNDy neurons, showed normal puberty while having a one-day longer estrous cycle and fewer pups than Kiss1-floxed controls. Notably, ovariectomized (OVX) Kiss1-floxed/Oprk1-Cre rats showed profound disruption of LH pulses in the presence of a diestrous level of estrogen but showed apparent LH pulses without estrogen treatment. Furthermore, Kiss1-floxed/Oprk1-Cre rats, with Kiss1 deleted in approximately half of AVPV kisspeptin neurons, showed a lower peak of the estrogen-induced LH surge than controls. These results suggest that arcuate and AVPV kisspeptin neurons expressing or having expressed Oprk1 have a role in maintaining normal GnRH pulse and surge generation, the normal length of the estrous cycle, and the normal offspring number in female rats.

摘要

促性腺激素释放激素（GnRH）脉冲和激增被认为分别由弓状核 kisspeptin/神经激肽 B/强啡肽 A（KNDy）神经元和前腹侧脑室下核（AVPV） kisspeptin 神经元产生。在雌性啮齿动物中，大多数 KNDy 和 AVPV kisspeptin 神经元表达κ-阿片受体（KOR，由 Oprk1 编码）。因此，本研究旨在使用 Kiss1 基因敲除/Oprk1-Cre 大鼠（其中 Kiss1 在表达或曾经表达 Oprk1/Cre 的细胞中被敲除），研究 kisspeptin 神经元中条件性 Oprk1 依赖性 Kiss1 缺失对促黄体生成素（LH）脉冲/激增和生育能力的影响。Kiss1 基因敲除/Oprk1-Cre 雌性大鼠的青春期正常，但发情周期长一天，产仔数比 Kiss1 基因敲除对照少。值得注意的是，卵巢切除（OVX） Kiss1 基因敲除/Oprk1-Cre 大鼠在存在去势水平雌激素的情况下表现出 LH 脉冲的严重中断，但在没有雌激素处理的情况下表现出明显的 LH 脉冲。此外，大约一半 AVPV kisspeptin 神经元中 Kiss1 缺失的 Kiss1 基因敲除/Oprk1-Cre 大鼠的雌激素诱导的 LH 激增峰值低于对照组。这些结果表明，表达或曾经表达 Oprk1 的弓状核和 AVPV kisspeptin 神经元在维持正常 GnRH 脉冲和激增产生、正常发情周期长度和正常后代数量方面发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f391/10665460/2492c8b54011/41598_2023_47222_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f391/10665460/dbaf3def610e/41598_2023_47222_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f391/10665460/471768dc4d5d/41598_2023_47222_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f391/10665460/e457273f0869/41598_2023_47222_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f391/10665460/a7deb00c4422/41598_2023_47222_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f391/10665460/4c8f39566d26/41598_2023_47222_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f391/10665460/2492c8b54011/41598_2023_47222_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f391/10665460/dbaf3def610e/41598_2023_47222_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f391/10665460/471768dc4d5d/41598_2023_47222_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f391/10665460/e457273f0869/41598_2023_47222_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f391/10665460/a7deb00c4422/41598_2023_47222_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f391/10665460/4c8f39566d26/41598_2023_47222_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f391/10665460/2492c8b54011/41598_2023_47222_Fig6_HTML.jpg

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Enkephalin-δ Opioid Receptor Signaling Mediates Glucoprivic Suppression of LH Pulse and Gluconeogenesis in Female Rats.
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