Norepinephrine Suppresses Gonadotropin-Releasing Hormone Neuron Excitability in the Adult Mouse

Han, Seungjin; Herbison, Allan E.

doi:10.1210/en.2007-1241

Cited by 47 publications

(32 citation statements)

References 34 publications

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“…We show here that dopamine exerts an unchanging, potent suppressive action on GnRH neuron firing across the estrous cycle with 64%, 56%, and 53% of GnRH neurons having their firing rate inhibited by approximately 75% in diestrous, proestrous, and estrous mice, respectively. This is a very similar situation to that found recently for the norepinephrine (NE) regulation of murine GnRH neurons where, despite evidence for gonadal steroid regulation of NE actions on LH secretion in vivo, the potent inhibitory effects of NE on GnRH neurons were relatively unchanged across the estrous cycle (29). Thus, it would appear that both NE and dopamine provide a steroid-independent inhibitory input to GnRH neurons in the mouse.…”

Section: Discussionsupporting

confidence: 84%

Dopamine Regulation of Gonadotropin-Releasing Hormone Neuron Excitability in Male and Female Mice

Liu

Herbison

2013

Endocrinology

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Numerous in vivo studies have shown that dopamine is involved in the regulation of LH secretion in mammals. However, the mechanisms through which this occurs are not known. In this study, we used green fluorescent protein-tagged GnRH neurons to examine whether and how dopamine may modulate the activity of adult GnRH neurons in the mouse. Bath-applied dopamine (10-80 M) potently inhibited the firing of approximately 50% of GnRH neurons. This resulted from direct postsynaptic inhibitory actions through D1-like, D2-like, or both receptors. Further, one third of GnRH neurons exhibited an increase in their basal firing rate after administration of SCH23390 (D1-like antagonist) and/or raclopride (D2-like antagonist) indicating tonic inhibition by endogenous dopamine in the brain slice. The role of dopamine in presynaptic modulation of the anteroventral periventricular nucleus (AVPV) ␥-aminobutyric acid/glutamate input to GnRH neurons was examined. Exogenous dopamine was found to presynaptically inhibit AVPV-evoked ␥-aminobutyric acid /glutamate postsynaptic currents in about 50% of GnRH neurons. These effects were, again, mediated by both D1-and D2-like receptors. Neither postsynaptic nor presynaptic actions of dopamine were found to be different between diestrous, proestrous, and estrous females, or males. Approximately 20% of GnRH neurons were shown to receive a dopaminergic input from AVPV neurons in male and female mice. Together, these observations show that dopamine is one of the most potent inhibitors of GnRH neuron excitability and that this is achieved through complex pre-and postsynaptic actions that each involve D1-and D2-like receptor activation. (Endocrinology 154: 340 -350, 2013)A lthough dopamine was among the first neurotransmitters investigated in relation to the control of the reproductive axis, there is little consensus regarding its effects on LH secretion or understanding of how it may impact upon GnRH neurons (1). Indeed, dopaminergic regulation of mammalian GnRH neurons is now something of a backwater and, with the exception of the A15 dopamine neuron influence on seasonality in sheep (2), there has been little progress in the field since the 1994 review by Kordon et al. (1).The lack of interest in the dopaminergic regulation of GnRH neurons is perhaps surprising given that the presence of tyrosine hydroxylase (TH)-immunoreactive terminals synapsing on GnRH neurons is one the most consistent ultrastructural features reported for GnRH neurons (3-5). Despite this evidence for direct dopaminergic inputs to GnRH neurons, the sites at which intracerebroventricular dopamine acts to modulate LH secretion in vivo, and the locations of dopaminergic inputs to GnRH neurons, are very unclear. For example, in rodents, dopamine appears to be able to act in the mediobasal hypothalamus and preoptic area, as well as zona incerta, to modulate LH secretion (6 -9).Studies in our laboratory have recently shown that a subpopulation of kisspeptin neurons located in the rostral periventricular area of the third ventric...

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Section: Discussionsupporting

confidence: 84%

Dopamine Regulation of Gonadotropin-Releasing Hormone Neuron Excitability in Male and Female Mice

Liu

Herbison

2013

Endocrinology

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“…The action of NMDA on cathecholaminergic neurons may therefore participate in the Kpindependent activation of GnRH/LH release. However, recent findings have shown that NE suppresses GnRH neuron excitability in the adult mouse (Han and Herbison, 2008) and force a reanalysis of existing models explaining the effects of NE on gonadotropin secretion. Moreover, NMDA receptors have been demonstrated in the brainstem in which catecholamine neurons, which project to the hypothalamus, could play a role in mediating the NMDA effects on GnRH release (Urbanski et al, 1997).…”

Section: Discussionmentioning

confidence: 98%

Kisspeptin Signaling Is Required for Peripheral But Not Central Stimulation of Gonadotropin-Releasing Hormone Neurons by NMDA

Tassigny¹,

Ackroyd²,

Chatzidaki³

et al. 2010

Journal of Neuroscience

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NMDA and kisspeptins can stimulate gonadotropin-releasing hormone (GnRH) release after peripheral or central administration in mice. To determine whether these agonists act independently or through a common pathway, we have examined their ability to stimulate GnRH/luteinizing hormone (LH) release after peripheral or central administration in Kiss1-or Gpr54 (Kiss1r)-null mutant mice. Peripheral injection of NMDA failed to stimulate GnRH/LH release in prepubertal or gonadally intact mutant male mice. Dual-labeling experiments indicated a direct activation of Kiss1-expressing neurons in the arcuate nucleus. In contrast, central injection of NMDA into the lateral ventricle increased plasma LH levels in both Kiss1 and Gpr54 mutant male mice similar to the responses in wild-type mice. Central injection of NMDA stimulated c-Fos expression throughout the hypothalamus but not in GnRH neurons, suggesting an action at the nerve terminals only. In contrast, kisspeptin-10 stimulated LH release after both central and peripheral injection but induced c-Fos expression in GnRH neurons only after central administration. Finally, central injection of NMDA induces c-Fos expression in catecholamine-and nitric oxide-producing neurons in the hypothalamus of mutant mice, indicating a possible kisspeptin-independent GnRH/LH release by NMDA through activation of these neurons. Thus, NMDA may act at both GnRH cell bodies (kisspeptin-independent) and nerve terminals (kisspeptin-dependent) in a dual way to participate in the GnRH/LH secretion in the male mouse.

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“…A recent study, however, suggests that the direct effect of norepinephrine on GnRH neurons is hyperpolarizing throughout the estrous cycle and in OVX mice (310), although the effect of norepinephrine in an OVXϩE treatment model was not investigated. Thus, future work is needed to determine how estradiol may modulate the GnRH neuron response to catecholamines, which of these effects may be direct on GnRH neurons, and which may involve other intermediaries.…”

Section: Catecholaminesmentioning

confidence: 99%

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

2010

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Ovarian steroids normally exert homeostatic negative feedback on GnRH release. During sustained exposure to elevated estradiol in the late follicular phase of the reproductive cycle, however, the feedback action of estradiol switches to positive, inducing a surge of GnRH release from the brain, which signals the pituitary LH surge that triggers ovulation. In rodents, this switch appears dependent on a circadian signal that times the surge to a specific time of day (e.g., late afternoon in nocturnal species). Although the precise nature of this daily signal and the mechanism of the switch from negative to positive feedback have remained elusive, work in the past decade has provided much insight into the role of circadian/diurnal and estradiol-dependent signals in GnRH/LH surge regulation and timing. Here we review the current knowledge of the neurobiology of the GnRH surge, in particular the actions of estradiol on GnRH neurons and their synaptic afferents, the regulation of GnRH neurons by fast synaptic transmission mediated by the neurotransmitters gamma-aminobutyric acid and glutamate, and the host of excitatory and inhibitory neuromodulators including kisspeptin, vasoactive intestinal polypeptide, catecholamines, neurokinin B, and RFamide-related peptides, that appear essential for GnRH surge regulation, and ultimately ovulation and fertility.

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Norepinephrine Suppresses Gonadotropin-Releasing Hormone Neuron Excitability in the Adult Mouse

Cited by 47 publications

References 34 publications

Dopamine Regulation of Gonadotropin-Releasing Hormone Neuron Excitability in Male and Female Mice

Dopamine Regulation of Gonadotropin-Releasing Hormone Neuron Excitability in Male and Female Mice

Kisspeptin Signaling Is Required for Peripheral But Not Central Stimulation of Gonadotropin-Releasing Hormone Neurons by NMDA

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

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