The Neurobiology of Preovulatory and Estradiol-Induced Gonadotropin-Releasing Hormone Surges

Christian, Catherine A.; Moenter, Suzanne M.

doi:10.1210/er.2009-0023

Cited by 259 publications

(198 citation statements)

References 370 publications

(117 reference statements)

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“…Together, these results suggest that NO-and kisspeptin-synthesizing neurons interact in synergy to coordinate the progression of the ovarian cycle, and thus reconcile the recent evidence that kisspeptin signaling plays a key role in the neuroendocrine control of reproduction (Funes et al, 2003;Seminara et al, 2003;d'Anglemont de Tassigny et al, 2007b;Dungan et al, 2007;Kauffman et al, 2007;Lapatto et al, 2007;Clarkson et al, 2008;Mayer et al, 2010;Mayer and Boehm, 2011), with the originally postulated role for NO in controlling GnRH secretion (Rettori et al, 1993;Mahachoklertwattana et al, 1994), the onset of the preovulatory GnRH/LH surge (Bonavera et al, 1993;Aguan et al, 1996;d'Anglemont de Tassigny et al, 2007a), and fertility (Gyurko et al, 2002). These findings also raise the exciting possibility that the estrogen-evoked kisspeptin-mediated activation of nNOS neurons in proestrus serves as an intermediate synchronizing switch for the GnRH system that enables the transition between pulsatile and peak release of GnRH (Christian and Moenter, 2010). NO could operate such a switch by acting either directly on GnRH neurons (Clasadonte et al, 2008) or on its trans-synaptic inputs (PieleckaFortuna et al, 2008;Zhang et al, 2009;Pielecka-Fortuna and Moenter, 2010), or both.…”

Section: Discussionmentioning

confidence: 92%

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: 92%

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

Parkash²,

et al. 2012

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“…Perhaps the lack of changes in GnRH firing activity is related to the fact that all recordings were made at the same time of day and using a saturating dose of PGE 2 . In addition to its postsynaptic effect on GnRH neurons, PGE 2 may also modulate the activity of steroid-sensitive afferent neuronal populations (49), including kisspeptin neurons that ensure coordinated progression of neuroendocrine events sustaining ovulatory cyclicity (50). The recent development of a mouse model that enables identification of kisspeptin neurons using fluorescent reporter genes (51) now renders these neurons amenable to scrutiny.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E ₂ release from astrocytes triggers gonadotropin-releasing hormone (GnRH) neuron firing via EP2 receptor activation

Clasadonte

Poulain

Hanchate

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

108

104

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Astrocytes in the hypothalamus release prostaglandin E 2 (PGE 2 ) in response to cell-cell signaling initiated by neurons and glial cells. Upon release, PGE 2 stimulates the secretion of gonadotropin-releasing hormone (GnRH), the neuropeptide that controls reproduction, from hypothalamic neuroendocrine neurons. Whether this effect on GnRH secretion is accompanied by changes in the firing behavior of these neurons is unknown. Using patch-clamp recording we demonstrate that PGE 2 exerts a dose-dependent postsynaptic excitatory effect on GnRH neurons. These effects are mimicked by an EP2 receptor agonist and attenuated by protein kinase A (PKA) inhibitors. The acute blockade of prostaglandin synthesis by indomethacin (INDO) or the selective inhibition of astrocyte metabolism by fluoroacetate (FA) suppresses the spontaneous firing activity of GnRH neurons in brain slices. Similarly, GnRH neuronal activity is reduced in mice with impaired astrocytic PGE 2 release due to defective erbB signaling in astrocytes. These results indicate that astrocyte-to-neuron communication in the hypothalamus is essential for the activity of GnRH neurons and suggest that PGE 2 acts as a gliotransmitter within the GnRH neurosecretory system. cyclooxygenase | glia-to-neuron signaling | luteinizing hormone-releasing hormone | preoptic region | fertility I t is increasingly clear that astrocytes play an important role in maintaining central nervous system function (1-3) and controlling key bodily processes, such as breathing (4), sleep (5), and reproduction (6). Because of their perivascular and interneuronal localization, astrocytes are well positioned to sense afferent neuronal and blood-borne signals and ideally suited for the temporal and spatial propagation of these signals (7-9). The activation of astrocytes leads to the release of gliotransmitters (8, 10) that trigger rapid responses in neighboring cells and thus contribute to the region-specific homeostatic regulation of neuronal function.In the hypothalamus, astrocytes regulate the secretory activity of neuroendocrine neurons (11)(12)(13)(14). A subset of such neurons secretes the decapeptide gonadotropin-releasing hormone (GnRH), which controls both the initiation of puberty and adult reproductive function. In rodents, GnRH neurons are mostly located in the preoptic region of the ventral forebrain. They project to the median eminence of the hypothalamus, where GnRH is released into the pituitary portal blood for delivery to the anterior pituitary. In the pituitary, GnRH elicits the secretion of luteinizing hormone and follicle-stimulating hormone, which stimulate gametogenesis and gonadal hormone secretion and thus support reproductive function. It is now clear that the secretory activity of GnRH neurons is controlled by both neuronal and glial input (12,13,15,16). Whereas glutamate is a key neurotransmitter involved in the transsynaptic activation of GnRH neurons (17, 18), prostaglandin E 2 (PGE 2 ) mediates cell-cell communication between astrocytes and GnRH neurons (6,19,20). A...

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“…The PGR is expressed in CCs and associated with the preovulatory stage in many mammals including mice (Hernandez-Gonzalez et al 2006), bovine (Mingoti et al 2002, Schoenfelder et al 2003, pig (Lucidi et al 2003), and human (Chian et al 1999). The changes in steroid output and sensitivity, especially in progesterone, could be required not only for mammalian oocyte final maturation, but also for ovulation and subsequent embryo survival (Wise et al 1994, Richards 2005, Christian & Moenter 2010, Lynch et al 2010. Interestingly, progesterone is also reported to be useful to the human sperm acrosome reaction (Teves et al 2009) and therefore could be useful for COCs in the fallopian tube.…”

Section: Steroid Biosynthesismentioning

confidence: 99%

Cumulus cell gene expression following the LH surge in bovine preovulatory follicles: potential early markers of oocyte competence

Assidi¹,

Dieleman²,

Sirard³

2010

Reproduction

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Cumulus cells (CCs) are essential for oocytes to reach full development competency and become fertilized. Many major functional properties of CCs are triggered by gonadotropins and governed by the oocyte. Consequently, cumulus may reflect oocyte quality and is often used for oocyte selection. The most visible function of CCs is their ability for rapid extracellular matrix expansion after the LH surge. Although unexplained, LH induces the final maturation and improves oocyte quality. To study the LH signaling and gene expression cascade patterns close to the germinal vesicle breakdown, bovine CCs collected at 2 h before and 6 h after the LH surge were hybridized to a custom-made microarray to better understand the LH genomic action and find differentially expressed genes associated with the LH-induced oocyte final maturation. Functional genomic analysis of the 141 overexpressed and 161 underexpressed clones was performed according to their molecular functions, gene networks, and cell compartments. Following real-time PCR validation of our gene lists, some interesting pathways associated with the LH genomic action on CCs and their possible roles in oocyte final maturation, ovulation, and fertilization are discussed. A list of early potential markers of oocyte competency in vivo and in vitro is thereafter suggested. These early biomarkers are a preamble to understand the LH molecular pathways that trigger the final oocyte competence acquisition process in bovine.

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The Neurobiology of Preovulatory and Estradiol-Induced Gonadotropin-Releasing Hormone Surges

Cited by 259 publications

References 370 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

Prostaglandin E ₂ release from astrocytes triggers gonadotropin-releasing hormone (GnRH) neuron firing via EP2 receptor activation

Cumulus cell gene expression following the LH surge in bovine preovulatory follicles: potential early markers of oocyte competence

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The Neurobiology of Preovulatory and Estradiol-Induced Gonadotropin-Releasing Hormone Surges

Cited by 259 publications

References 370 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

Prostaglandin E 2 release from astrocytes triggers gonadotropin-releasing hormone (GnRH) neuron firing via EP2 receptor activation

Cumulus cell gene expression following the LH surge in bovine preovulatory follicles: potential early markers of oocyte competence

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Prostaglandin E ₂ release from astrocytes triggers gonadotropin-releasing hormone (GnRH) neuron firing via EP2 receptor activation