The distribution of hypothalamic nitric oxide synthase mRNA in relation to gonadotrophin-releasing hormone neurons

Grossman, Ashley; Rossmanith, W. G.; Kabigting, E B; Cadd, G. G.; Clifton, Don K.; Steiner, Robert A.

doi:10.1677/joe.0.140r005

Cited by 83 publications

(44 citation statements)

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“…Since NO cannot be stored in synaptic vesicles, unlike other neurotransmitters, mechanisms that regulate its synthesis in time and space are crucial in determining its biological effect (Garthwaite, 2008). In the mouse (Clasadonte et al, 2008;present study), as in the rat (Grossman et al, 1994;Herbison et al, 1996), GnRH neurons are surrounded by NO-synthesizing neurons in the basal forebrain, one of the major sites of NOS expression in the CNS (Bredt et al, 1991;Yamada et al, 1996;Edelmann et al, 2007). The production of neuronal NO in the vicinity of GnRH neurons is tightly regulated by estrogens (d 'Anglemont de Tassigny et al, 2007a;Parkash et al, 2010) and has been shown to directly modulate GnRH neuronal activity (Clasadonte et al, 2008).…”

Section: Discussionmentioning

confidence: 94%

Kisspeptin-GPR54 Signaling in Mouse NO-Synthesizing Neurons Participates in the Hypothalamic Control of Ovulation

Parkash²,

et al. 2012

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Reproduction is controlled in the brain by a neural network that drives the secretion of gonadotropin-releasing hormone (GnRH).Various permissive homeostatic signals must be integrated to achieve ovulation in mammals. However, the neural events controlling the timely activation of GnRH neurons are not completely understood. Here we show that kisspeptin, a potent activator of GnRH neuronal activity, directly communicates with neurons that synthesize the gaseous transmitter nitric oxide (NO) in the preoptic region to coordinate the progression of the ovarian cycle. Using a transgenic Gpr54-null IRES-LacZ knock-in mouse model, we demonstrate that neurons containing neuronal NO synthase (nNOS), which are morphologically associated with kisspeptin fibers, express the kisspeptin receptor GPR54 in the preoptic region, but not in the tuberal region of the hypothalamus. The activation of kisspeptin signaling in preoptic neurons promotes the activation of nNOS through its phosphorylation on serine 1412 via the AKT pathway and mimics the positive feedback effects of estrogens. Finally, we show that while NO release restrains the reproductive axis at stages of the ovarian cycle during which estrogens exert their inhibitory feedback, it is required for the kisspeptin-dependent preovulatory activation of GnRH neurons. Thus, interactions between kisspeptin and nNOS neurons may play a central role in regulating the hypothalamic-pituitary-gonadal axis in vivo.

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Section: Discussionmentioning

confidence: 94%

Kisspeptin-GPR54 Signaling in Mouse NO-Synthesizing Neurons Participates in the Hypothalamic Control of Ovulation

Parkash²,

et al. 2012

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“…both the MPOA and ME-ARC are included in several areas of the hypothalamus where significant NOS activity can be detected [22]. The anatomical findings that GnRH neurons in the MPOA are frequently surrounded by NOS-positive neurons and fibers suggest that NO may regulate GnRH neurons in a paracrine manner [23, 24]. Furthermore, López et al [25]demonstrated colocalization of neuronal NOS and GnRH neurons.…”

Section: Discussionmentioning

confidence: 99%

A Comparative Study of the Effects of Nitric Oxide and Carbon Monoxide on the in vivo Release of Gonadotropin-Releasing Hormone and Neuropeptide Y from Rat Hypothalamus during the Estradiol-Induced Luteinizing Hormone Surge: Estimation by Push-Pull Perfusion

et al. 1999

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Recent evidence suggests that nitric oxide (NO), a free radical gas, plays an important role in regulating the function of a variety of neuroendocrine systems. With respect to the hypothalamo-pituitary-gonadal axis, a stimulatory effect of NO on the release of gonadotropin-releasing hormone (GnRH) from rat hypothalamus has been demonstrated in vitro. However, no previous study has reported NO-stimulated secretion of GnRH from in vivo hypothalamus, and also the precise cellular site of action of NO within the GnRH neuronal system remains to be elucidated. In the present study, utilizing the push-pull perfusion technique of rat hypothalamus, we examined the effect of L-arginine (L-Arg), an NO donor, on the release of GnRH, neuropeptide Y and cyclic GMP (c-GMP), which is a pivotal second messenger molecule of the NO system. For comparison, we also examined the effect of carbon monoxide (CO), another putative gaseous neurotransmitter, using hematin, a CO donor. During the period of 11.00–18.00 h, we collected blood and hypothalamic perfusates from ovariectomized adult rats that had been implanted with an estradiol capsule 2 days before. During the entire period of observation, L-Arg (1.0 or 10 mM), hematin (10 or 100 µM) or artificial cerebrospinal fluid alone (as the control) was infused into the medial preoptic area (MPOA) where there are cell bodies of GnRH neurons, or the median eminence-arcuate nucleus complex (ME-ARC) where axon terminals of GnRH neurons are localized. Although 10 mM of L-Arg significantly stimulated GnRH and c-GMP, but not neuropeptide Y, levels in both the MPOA and ME-ARC, GnRH and c-GMP in the ME-ARC were already increased by 1.0 mM of L-Arg. By contrast, both concentrations of hematin were without effect at either site of the hypothalamus. This study is the first to demonstrate that NO is capable of stimulating GnRH release from rat hypothalamus in vivo. Our data also suggests that both cell bodies and axon terminals of GnRH neurons may be sites of action of NO. Our data do not support a previous study by other investigators that reported a stimulatory effect of CO on the GnRH release.

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“…NO is involved in neuroendocrine regulation in that generation of NO is capable of releasing gonadotrophin-releasing hormone (GnRH) from hypothalamic neurons (Lopez et al, 1997). The importance of NOS in this tissue is further substantiated by the finding of adjacent expression of NOS to GnRH in closely apposed neurons (Grossman et al, 1994), or their colocalization in immortalized neurons (Bhat et al, 1995). Because GnRH is also an important neuroendocrine regulator in the placenta, we have speculated that NO and, by inference, NOS may also play a pivotal role in the human placenta.…”

Section: Introductionmentioning

confidence: 99%

Expression and functional analysis of endothelial nitric oxide synthase (eNOS) in human placenta

Rossmanith

Hoffmeister²,

Wolfahrt³

et al. 1999

Molecular Human Reproduction

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We have investigated the expression and localization of endothelium-derived nitric oxide synthase (eNOS) and the effect of eNOS on placental human chorionic gonadotrophin (HCG) release. eNOS mRNA was found to be expressed in all tissues, with its expression significantly (P < 0.05) increased across gestation. Compared to normal term gestation, placentae from term pregnancies with fetal retardation, or maternal diabetes, but not with maternal hypertension, displayed significantly more (P < 0.05) eNOS mRNA. By immunocytochemistry, we found staining for eNOS in both the cyto-and syncytiotrophoblasts of first trimester and a loss of cytotrophoblast eNOS staining in term placentae, while syncytiotrophoblasts at term were strongly eNOS positive. Additional staining was found in endothelium surrounding the vascular tree. HCG was found to colocalize with eNOS in trophoblasts, but not in endothelia. When placental explants were perifused, exposure to the NOS substrate, the NO donor, l-arginine and trinitroglycerol evoked a prompt, albeit transient, increase of HCG release. The NOS inhibitor delayed, but did not block arginine-induced HCG release. Thus, eNOS is expressed in the human placenta at increasing levels during gestation with further increases during some pathological conditions. A role for NO in the acute endocrine modulation of the placenta is suggested by the colocalization of eNOS with HCG in human trophoblasts and the prompt secretion of HCG in response to agents which increase NO concentrations.

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The distribution of hypothalamic nitric oxide synthase mRNA in relation to gonadotrophin-releasing hormone neurons

Cited by 83 publications

References 0 publications

Kisspeptin-GPR54 Signaling in Mouse NO-Synthesizing Neurons Participates in the Hypothalamic Control of Ovulation

Kisspeptin-GPR54 Signaling in Mouse NO-Synthesizing Neurons Participates in the Hypothalamic Control of Ovulation

A Comparative Study of the Effects of Nitric Oxide and Carbon Monoxide on the in vivo Release of Gonadotropin-Releasing Hormone and Neuropeptide Y from Rat Hypothalamus during the Estradiol-Induced Luteinizing Hormone Surge: Estimation by Push-Pull Perfusion

Expression and functional analysis of endothelial nitric oxide synthase (eNOS) in human placenta

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