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

Liu, Xinhuai; Herbison, Allan E.

doi:10.1210/en.2012-1602

Cited by 91 publications

(60 citation statements)

References 31 publications

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“…GABA co-expression patterns appeared similar across both dorsal and ventral populations, suggesting similar co-expression proportions for both TIDA and A12 neurons. Dopamine has been shown to have potent inhibitory effects on GnRH neuron excitability [53] , and there is substantial ultrastructural evidence for dopamine synaptic inputs to GnRH neurons [54][55][56] ; however, it is questionable whether this input arises from the ARN [57] . Interestingly, the present study found that TH-positive neurons in males were more likely to be GABAergic than in females, a sex difference that has not been previously reported in the ARN.…”

Section: Discussionmentioning

confidence: 99%

Defining Subpopulations of Arcuate Nucleus GABA Neurons in Male, Female, and Prenatally Androgenized Female Mice

et al. 2016

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Background/Aims: Arcuate nucleus (ARN) γ-aminobutyric acid (GABA) neurons are implicated in many critical homeostatic mechanisms, from food intake to fertility. To determine the functional relevance of ARN GABA neurons, it is essential to define the neurotransmitters co-expressed with and potentially co-released from ARN GABA neurons. Methods: The present study investigated the expression of markers of specific signaling molecules by ARN GABA neurons in brain sections from male, female, and, in some cases, prenatally androgen-treated (PNA) female, vesicular GABA transporter (VGaT)-ires-Cre/tdTomato reporter mice. Immunofluorescence for kisspeptin, β-endorphin, neuropeptide Y (NPY), tyrosine hydroxylase (TH) and neuronal nitric oxide synthase (nNOS) was detected by confocal microscopy, and co-localization with tdTomato VGaT reporter expression throughout the ARN was quantified. Results: GABA neurons rarely co-localized with kisspeptin (<2%) or β-endorphin (<1%), and only a small proportion of kisspeptin (∼10%) or β-endorphin (∼3%) neurons co-localized with VGaT in male and female mice. In contrast, one-third of ARN GABA neurons co-localized with NPY, and nearly all NPY neurons (>95%) co-localized with VGaT across groups. Both TH and nNOS labeling was co-localized with ∼10% of ARN GABA neurons. The proportion of TH neurons co-localized with VGaT was significantly greater in males than either control or PNA females, and the proportion of nNOS neurons co-localizing VGaT was higher in control and PNA females compared with males. Conclusion: These data highlight NPY as a significant subpopulation of ARN GABA neurons, demonstrate no significant impact of PNA on signal co-expression, and, for the first time, show sexually dimorphic co-expression patterns of TH and nNOS with ARN GABA neurons.

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Section: Discussionmentioning

confidence: 99%

Defining Subpopulations of Arcuate Nucleus GABA Neurons in Male, Female, and Prenatally Androgenized Female Mice

et al. 2016

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“…Together, these results strongly suggest that dopaminergic inhibition of GnRH1 neurons is achieved via D2R-mediated opening of potassium channels. Similarly, dopamine regulates hypothalamic GnRH neurons in mice via both D1Rs and D2Rs, the latter also via potassium channels (Liu and Herbison, 2013). The identity of the potassium channel involved in D2R-mediated inhibition of mammalian and fish GnRH neurons is unknown, although candidates include G-protein-coupled inwardly rectifying and ATP-sensitive channels.…”

Section: D2r Agonists Directly Inhibit Gnrh1 Neuronsmentioning

confidence: 99%

Dopaminergic inhibition of gonadotropin-releasing hormone neurons in the cichlid fish,Astatotilapia burtoni

Bryant

Greenwood

Juntti

et al. 2016

Journal of Experimental Biology

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Dopamine regulates reproduction in part by modulating neuronal activity within the hypothalamic-pituitary-gonadal (HPG) axis. Previous studies suggested numerous mechanisms by which dopamine exerts inhibitory control over the HPG axis, ultimately changing the levels of sex steroids that regulate reproductive behaviors. However, it is not known whether these mechanisms are conserved across vertebrate species. In particular, it is unknown whether mechanisms underlying dopaminergic control of reproduction are shared between mammals and teleost fish. In mammals, dopamine directly inhibits gonadotropin-releasing hormone (GnRH1) hypothalamic neurons, the gatekeepers for activation of the HPG axis. Here, we demonstrate, for the first time in teleost fish, dopaminergic control of GnRH1 neurons via direct dopamine type-2-like receptor (D2R)-mediated inhibition within the hypothalamus. These results suggest that direct dopaminergic control of GnRH1 neurons via interactions in the hypothalamus is not exclusive to tetrapod reproductive control, but is likely conserved across vertebrate species.

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“…Dopamine has been shown to be one of the most potent inhibitors of GnRH neuronal excitation (29). To determine when kisspeptin neurons in the AVPV start to pro- Blue arrowheads indicate estrogen-sensitive kisspeptin neurons that are not synaptically connected to GnRH neurons.…”

Section: Increase In Dopaminergic Avpv Kisspeptin Neurons During Pubertymentioning

confidence: 99%

Specialized Subpopulations of Kisspeptin Neurons Communicate With GnRH Neurons in Female Mice

et al. 2015

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The neuropeptide kisspeptin is a potent stimulator of GnRH neurons and has been implicated as a major regulator of the hypothalamus-pituitary-gonadal axis. There are mainly two anatomically segregated populations of neurons that express kisspeptin in the female hypothalamus: one in the anteroventral periventricular nucleus (AVPV) and the other in the arcuate nucleus (ARC). Distinct roles have been proposed for AVPV and ARC kisspeptin neurons during reproductive maturation and in mediating estrogen feedback on the hypothalamus-pituitary-gonadal axis in adults. Despite their pivotal role in the regulation of reproductive physiology, little is known about kisspeptin neuron connectivity. Although previous data suggest heterogeneity within the AVPV and ARC kisspeptin neuron populations, how many and which of these potential kisspeptin neuron subpopulations are actually communicating with GnRH neurons is not known. Here we used a combinatorial genetic transsynaptic tracing strategy to start to analyze the connectivity of individual kisspeptin neurons with the GnRH neuron population in female mice with a single-cell resolution. We find that only subsets of AVPV and ARC kisspeptin neurons are synaptically connected with GnRH neurons. We demonstrate that the majority of kisspeptin neurons within the AVPV and ARC does not communicate with GnRH neurons. Furthermore, we show that all kisspeptin neurons within the AVPV connected to GnRH neurons are estrogen sensitive and that most of these express tyrosine hydroxylase. Our data demonstrate functional specialization within the two kisspeptin neuron populations.

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

Cited by 91 publications

References 31 publications

Defining Subpopulations of Arcuate Nucleus GABA Neurons in Male, Female, and Prenatally Androgenized Female Mice

Defining Subpopulations of Arcuate Nucleus GABA Neurons in Male, Female, and Prenatally Androgenized Female Mice

Dopaminergic inhibition of gonadotropin-releasing hormone neurons in the cichlid fish,Astatotilapia burtoni

Specialized Subpopulations of Kisspeptin Neurons Communicate With GnRH Neurons in Female Mice

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