The Arcuate Nucleus Mediates Facilitating Effect of Estrogen on Glutamate-Induced In Vitro GnRH Release from Nerve Terminals of Female Rats.

Murahashi, Kumiko; Tsukahara, Shinji; Tsukamura, Hiroko

doi:10.1262/jrd.48.183

Cited by 4 publications

(3 citation statements)

References 41 publications

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“…In addition to AVPV kisspeptin neurons, ARC kisspeptin neurons may mediate the effect of GnRH(1-5) challenge to enhance the surgelike increase in LH release. Involvement of ARC kisspeptin neurons and hypothalamic glutamatergic neurons in GnRH/LH surge generation has been suggested as follows: an increase in c-Fos expressions in the ARC kisspeptin neurons was shown prior to GnRH/LH surge in rats [24] and ewe [25,26]; female rats with attenuated ARC kisspeptin neurons by neurotoxin showed limited magnitude of LH surge [27]; an increase in in vivo glutamate release prior to LH surge is evident in the medio-basal hypothalamus including the ARC in female rats [28]; glutamate strongly stimulated in vitro GnRH release from the ARC-median eminence fragment of female rats, but the stimulating effect was moderate with the fragment without the ARC [29]. In rodents, it is considered that majority of ARC kisspeptin neurons are glutamatergic ones as well, because nearly 90% of ARC kisspeptin neurons expressed glutamate transporter mRNA in mice [30].…”

Section: Discussionmentioning

confidence: 98%

GnRH(1-5), a metabolite of gonadotropin-releasing hormone, enhances luteinizing hormone release <i>via</i> activation of kisspeptin neurons in female rats

et al. 2020

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Accumulating evidence suggests that kisspeptin neurons in the arcuate nucleus (ARC), which coexpress neurokinin B and dynorphin, are involved in gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) pulse generation, while the anteroventral periventricular nucleus (AVPV) kisspeptin neurons are responsible for GnRH/LH surge generation. The present study aims to examine whether GnRH(1-5), a GnRH metabolite, regulates LH release via kisspeptin neurons. GnRH(1-5) was intracerebroventricularly injected to ovariectomized and estrogen-treated Wistar-Imamichi female rats. Immediately after the central GnRH(1-5) administration at 2 nmol, plasma LH concentration increased, resulting in significantly higher levels of the area under the curve and baseline of plasma LH concentrations compared to vehicle-injected controls. On the other hand, in Kiss1 knockout rats, GnRH(1-5) administration failed to affect LH secretion, suggesting that the facilitatory effect of GnRH(1-5) on LH release is mediated by kisspeptin neurons. Double in situ hybridization (ISH) for Kiss1 and Gpr101, a GnRH(1-5) receptor gene, revealed that few Kiss1-expressing cells coexpress Gpr101 in both ARC and AVPV. On the other hand, double ISH for Gpr101 and Slc17a6, a glutamatergic marker gene, revealed that 29.2% of ARC Gpr101-expressing cells coexpress Slc17a6. Further, most of the AVPV and ARC Kiss1-expressing cells coexpress Grin1, a gene encoding a subunit of NMDA receptor. Taken together, these results suggest that the GnRH(1-5)-GPR101 signaling facilitates LH release via indirect activation of kisspeptin neurons and that glutamatergic neurons may mediate the signaling. This provides a new aspect of kisspeptin-and GnRH-neuronal communication with the presence of stimulation from GnRH to kisspeptin neurons in female rats.

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Section: Discussionmentioning

confidence: 98%

GnRH(1-5), a metabolite of gonadotropin-releasing hormone, enhances luteinizing hormone release <i>via</i> activation of kisspeptin neurons in female rats

et al. 2020

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“…We determined whether kisspeptin mediates the effects of several stimulatory neurotransmitters on LH release. The effects of peripheral injection of monosodium glutamate (MSG), an excitatory amino acid, on LH secretion were determined because NMDA, kainate and AMPA stimulated GnRH release from the cultured median eminence and/or ARC‐median eminence tissue . Because the median eminence is out of the blood–brain barrier, MSG was administered intravenously.…”

Section: Methodsmentioning

confidence: 99%

Lack of Pulse and Surge Modes and Glutamatergic Stimulation of Luteinising Hormone Release in Kiss1 Knockout Rats

Uenoyama

Nakamura

Hayakawa

et al. 2015

J Neuroendocrinology

107

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Kisspeptin, encoded by the Kiss1 gene, has attracted attention as a key candidate neuropeptide in controlling puberty and reproduction via regulation of gonadotrophin-releasing hormone (GnRH) secretion in mammals. Pioneer studies with Kiss1 or its cognate receptor Gpr54 knockout (KO) mice showed the indispensable role of kisspeptin-GPR54 signalling in the control of animal reproduction, although detailed analyses of gonadotrophin secretion, especially pulsatile and surge-mode of luteinising hormone (LH) secretion, were limited. Thus, in the present study, we have generated Kiss1 KO rats aiming to evaluate a key role of kisspeptin in governing reproduction via pulse and surge modes of GnRH/LH secretion. Kiss1 KO male and female rats showed a complete suppression of pulsatile LH secretion, which is responsible for folliculogenesis and spermatogenesis, and an absence of puberty and atrophic gonads. Kiss1 KO female rats showed no spontaneous LH/follicle-stimulating hormone surge and an oestrogen-induced LH surge, suggesting that the GnRH surge generation system, which is responsible for ovulation, does not function without kisspeptin. Furthermore, challenge of major stimulatory neurotransmitters, such as monosodium glutamate, NMDA and norepinephrine, failed to stimulate LH secretion in Kiss1 KO rats, albeit they stimulated LH release in wild-type controls. Taken together, the results of the present study confirm that kisspeptin plays an indispensable role in generating two modes (pulse and surge) of GnRH/gonadotrophin secretion to regulate puberty onset and normal reproductive performance. In addition, the present study suggests that kisspeptin neurones play a critical role as a hub integrating major stimulatory neural inputs to GnRH neurones, using newly established Kiss1 KO rats, which serve as a useful model for detailed analysis of hormonal profiles.

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“…N-methyl-D-aspartate (NMDA), an ionotropic glutamatergic receptor agonist, immediately stimulates LH secretion in wild-type female rats but not in Kiss1 knockout rats [ 21 ]. Furthermore, our previous studies have revealed that the expression of NR1 gene ( Grin1 ), a subunit of the NMDA receptor, can be observed in most ARC kisspeptin neurons in female rats [ 22 ], and glutamate treatment largely enhanced in vitro GnRH release from the ARC-median eminence tissue taken from female rats [ 23 ]. Notably, previous studies have indicated the suppressive effect of SST-SSTR2 signaling on glutamate release from glutamatergic neurons in the cerebral cortex and retina of mice [ 24 , 25 ] and in the hippocampus and basal forebrain of rats [ 26 , 27 ].…”

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confidence: 99%

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

et al. 2022

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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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The Arcuate Nucleus Mediates Facilitating Effect of Estrogen on Glutamate-Induced In Vitro GnRH Release from Nerve Terminals of Female Rats.

Cited by 4 publications

References 41 publications

GnRH(1-5), a metabolite of gonadotropin-releasing hormone, enhances luteinizing hormone release <i>via</i> activation of kisspeptin neurons in female rats

GnRH(1-5), a metabolite of gonadotropin-releasing hormone, enhances luteinizing hormone release <i>via</i> activation of kisspeptin neurons in female rats

Lack of Pulse and Surge Modes and Glutamatergic Stimulation of Luteinising Hormone Release in Kiss1 Knockout Rats

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

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