Central somatostatin-somatostatin receptor 2 signaling mediates lactational suppression of luteinizing hormone release via the inhibition of glutamatergic interneurons during late lactation in rats

Reproductive function is suppressed during lactation owing to the suckling-induced suppression of the kisspeptin gene (Kiss1) expression in the arcuate nucleus (ARC) and subsequent suppression of luteinizing hormone (LH) release. Our previous study revealed that somatostatin (SST) neurons mediate su...

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Main Authors: Arisa SUGIMOTO, Hitomi TSUCHIDA, Mayuko NAGAE, Naoko INOUE, Yoshihisa UENOYAMA, Hiroko TSUKAMURA
Format: Article
Language:English
Published: The Society for Reproduction and Development 2022-03-01
Series:The Journal of Reproduction and Development
Subjects:
Online Access:https://www.jstage.jst.go.jp/article/jrd/68/3/68_2022-009/_pdf/-char/en
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author Arisa SUGIMOTO
Hitomi TSUCHIDA
Mayuko NAGAE
Naoko INOUE
Yoshihisa UENOYAMA
Hiroko TSUKAMURA
author_facet Arisa SUGIMOTO
Hitomi TSUCHIDA
Mayuko NAGAE
Naoko INOUE
Yoshihisa UENOYAMA
Hiroko TSUKAMURA
author_sort Arisa SUGIMOTO
collection DOAJ
description Reproductive function is suppressed during lactation owing to the suckling-induced suppression of the kisspeptin gene (Kiss1) expression in the arcuate nucleus (ARC) and subsequent suppression of luteinizing hormone (LH) release. Our previous study revealed that somatostatin (SST) neurons mediate suckling-induced suppression of LH release via SST receptor 2 (SSTR2) in ovariectomized lactating rats during early lactation. This study examined whether central SST-SSTR2 signaling mediates the inhibition of ARC Kiss1 expression and LH release in lactating rats during late lactation and whether the inhibition of glutamatergic neurons, stimulators of LH release, is involved in the suppression of LH release mediated by central SST-SSTR2 signaling in lactating rats. A central injection of the SSTR2 antagonist CYN154806 (CYN) significantly increased ARC Kiss1 expression in lactating rats on day 16 of lactation. Dual in situ hybridization revealed that few ARC Kiss1-positive cells co-expressed Sstr2, and some of the ARC Slc17a6 (a glutamatergic neuronal marker)-positive cells co-expressed Sstr2. Furthermore, almost all ARC Kiss1-positive cells co-expressed Grin1, a subunit of N-methyl-D-aspartate (NMDA) receptors. The numbers of Slc17a6/Sstr2 double-labeled and Slc17a6 single-labeled cells were significantly lower in lactating dams than in non-lactating rats whose pups had been removed after parturition. A central injection of an NMDA antagonist reversed the CYN-induced increase in LH release in lactating rats. Overall, these results suggest that central SST-SSTR2 signaling, at least partly, mediates the suppression of ARC Kiss1 expression and LH release by inhibiting ARC glutamatergic interneurons in lactating rats.
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spelling doaj.art-52e62a9dbb8643b9a68314c018016f8c2023-11-08T05:06:30ZengThe Society for Reproduction and DevelopmentThe Journal of Reproduction and Development0916-88181348-44002022-03-0168319019710.1262/jrd.2022-009jrdCentral somatostatin-somatostatin receptor 2 signaling mediates lactational suppression of luteinizing hormone release via the inhibition of glutamatergic interneurons during late lactation in ratsArisa SUGIMOTO0Hitomi TSUCHIDA1Mayuko NAGAE2Naoko INOUE3Yoshihisa UENOYAMA4Hiroko TSUKAMURA5Graduate School of Bioagricultural Sciences, Nagoya University, Aichi 464-8601, JapanGraduate School of Bioagricultural Sciences, Nagoya University, Aichi 464-8601, JapanGraduate School of Bioagricultural Sciences, Nagoya University, Aichi 464-8601, JapanGraduate School of Bioagricultural Sciences, Nagoya University, Aichi 464-8601, JapanGraduate School of Bioagricultural Sciences, Nagoya University, Aichi 464-8601, JapanGraduate School of Bioagricultural Sciences, Nagoya University, Aichi 464-8601, JapanReproductive function is suppressed during lactation owing to the suckling-induced suppression of the kisspeptin gene (Kiss1) expression in the arcuate nucleus (ARC) and subsequent suppression of luteinizing hormone (LH) release. Our previous study revealed that somatostatin (SST) neurons mediate suckling-induced suppression of LH release via SST receptor 2 (SSTR2) in ovariectomized lactating rats during early lactation. This study examined whether central SST-SSTR2 signaling mediates the inhibition of ARC Kiss1 expression and LH release in lactating rats during late lactation and whether the inhibition of glutamatergic neurons, stimulators of LH release, is involved in the suppression of LH release mediated by central SST-SSTR2 signaling in lactating rats. A central injection of the SSTR2 antagonist CYN154806 (CYN) significantly increased ARC Kiss1 expression in lactating rats on day 16 of lactation. Dual in situ hybridization revealed that few ARC Kiss1-positive cells co-expressed Sstr2, and some of the ARC Slc17a6 (a glutamatergic neuronal marker)-positive cells co-expressed Sstr2. Furthermore, almost all ARC Kiss1-positive cells co-expressed Grin1, a subunit of N-methyl-D-aspartate (NMDA) receptors. The numbers of Slc17a6/Sstr2 double-labeled and Slc17a6 single-labeled cells were significantly lower in lactating dams than in non-lactating rats whose pups had been removed after parturition. A central injection of an NMDA antagonist reversed the CYN-induced increase in LH release in lactating rats. Overall, these results suggest that central SST-SSTR2 signaling, at least partly, mediates the suppression of ARC Kiss1 expression and LH release by inhibiting ARC glutamatergic interneurons in lactating rats.https://www.jstage.jst.go.jp/article/jrd/68/3/68_2022-009/_pdf/-char/englutamatekisspeptinlactationluteinizing hormonesomatostatin
spellingShingle Arisa SUGIMOTO
Hitomi TSUCHIDA
Mayuko NAGAE
Naoko INOUE
Yoshihisa UENOYAMA
Hiroko TSUKAMURA
Central somatostatin-somatostatin receptor 2 signaling mediates lactational suppression of luteinizing hormone release via the inhibition of glutamatergic interneurons during late lactation in rats
The Journal of Reproduction and Development
glutamate
kisspeptin
lactation
luteinizing hormone
somatostatin
title Central somatostatin-somatostatin receptor 2 signaling mediates lactational suppression of luteinizing hormone release via the inhibition of glutamatergic interneurons during late lactation in rats
title_full Central somatostatin-somatostatin receptor 2 signaling mediates lactational suppression of luteinizing hormone release via the inhibition of glutamatergic interneurons during late lactation in rats
title_fullStr Central somatostatin-somatostatin receptor 2 signaling mediates lactational suppression of luteinizing hormone release via the inhibition of glutamatergic interneurons during late lactation in rats
title_full_unstemmed Central somatostatin-somatostatin receptor 2 signaling mediates lactational suppression of luteinizing hormone release via the inhibition of glutamatergic interneurons during late lactation in rats
title_short Central somatostatin-somatostatin receptor 2 signaling mediates lactational suppression of luteinizing hormone release via the inhibition of glutamatergic interneurons during late lactation in rats
title_sort central somatostatin somatostatin receptor 2 signaling mediates lactational suppression of luteinizing hormone release via the inhibition of glutamatergic interneurons during late lactation in rats
topic glutamate
kisspeptin
lactation
luteinizing hormone
somatostatin
url https://www.jstage.jst.go.jp/article/jrd/68/3/68_2022-009/_pdf/-char/en
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