Comparative analysis of kisspeptin-immunoreactivity reveals genuine differences in the hypothalamic Kiss1 systems between rats and mice

Overgaard, Agnete; Tena‐Sempere, Manuel; Franceschini, Isabelle; Desroziers, Elodie; Simonneaux, Valérie; Mikkelsen, Jens D.

doi:10.1016/j.peptides.2013.04.013

Cited by 44 publications

(50 citation statements)

References 42 publications

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“…Prior colchicine treatment ensured that neuropeptides were detectable in neuronal cell bodies. The distribution patterns reported here for GABA and other neuronal markers are similar to mRNA expression patterns previously reported by the Allen Brain Institute (http://www.brain-map.org), and our findings are in line with previous reports of the immunoreactive detection of kisspeptin [32] , NPY [33,34] , TH [34,35] , β-endorphin [35] , and nNOS [36] in the mouse. In conjunction with the previously reported characterization of these antisera and the absence of labeling in primary antibody omission controls here, these data support our ability to accurately identify the neuronal expression of these peptidergic, catecholaminergic, and gaseous neurotransmitters in the mouse brain.…”

Section: Discussionsupporting

confidence: 92%

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: Discussionsupporting

confidence: 92%

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

et al. 2016

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“…Our previous study, and several other studies, have reported that kiss-ir cell bodies in the AVPV of nonlactating rats are low or non-detectable (Iijima et al 2011, Overgaard et al 2013. However, in this study, kiss-ir cell bodies were detected in all the groups, even in the normal lactating group in which Kiss1 mRNA was suppressed.…”

Section: Discussioncontrasting

confidence: 86%

“…The numbers of the kiss-ir neurons are relatively smaller than that of Kiss1 mRNA expressing neurons observed in the in situ hybridization in all the experimental groups. It should be noted that such discrepancies between the Kiss1 mRNA and the kisspeptin peptide have been reported in several studies (Iijima et al 2011, Overgaard et al 2013. These discrepancies could be due to the combination of several reasons including the turnover rate of the molecule, axonal transport of the peptide, and the accumulation in the neuronal cell bodies.…”

Section: Discussionmentioning

confidence: 92%

Rapid modulation of hypothalamic Kiss1 levels by the suckling stimulus in the lactating rat

Higo¹,

Aikawa²,

Iijima³

et al. 2015

Journal of Endocrinology

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In mammals, lactation suppresses GnRH/LH secretion resulting in transient infertility. In rats, GnRH/LH secretion is rescued within 18-48 h after pup separation (PS) and rapidly re-suppressed by subsequent re-exposure of pups. To elucidate the mechanisms underlying these rapid modulations, changes in the expression of kisspeptin, a stimulator of GnRH secretion, in several lactating conditions (normal-lactating; 4-h PS; 18-h PS; 4-h PS C1-h re-exposure of pups; non-lactating) were examined using in situ hybridization. PS for 4 h or 18 h increased Kiss1 expressing neurons in both the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (ARC), and subsequent exposure of pups re-suppressed Kiss1 in the AVPV. A change in Kiss1 expression was observed prior to the reported time of the change in GnRH/LH, indicating that the change in GnRH/LH results from changes in kisspeptin. We further examined the mechanisms underlying the rapid modulation of Kiss1. We first investigated the possible involvement of ascending sensory input during the suckling stimulus. Injection of the anterograde tracer to the subparafascicular parvocellular nucleus (SPFpc) in the midbrain, which relays the suckling stimulus, revealed direct neuronal connections between the SPFpc and kisspeptin neurons in both the AVPV and ARC. We also examined the possible involvement of prolactin (PRL). Administration of PRL for 1 h suppressed Kiss1 expression in the AVPV but not in the ARC. These results indicate that suckling stimulus rapidly modulates Kiss1 expression directly via neuronal connections and indirectly through serum PRL, resulting in modulation in GnRH/LH secretion.

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“…Rats were transcardially perfused between 10 AM and 12 PM 3B). Kisspeptin labeling in the AVPV was characterized by the presence of kisspeptin-ir fibers and practically no labeling of neuronal cells bodies, as has been reported previously for the female rat (51). In addition, the percentage of kisspeptin-ir area in the AVPV did not differ among the experimental groups (P ϭ .35) ( Figure 3C).…”

Section: Effect Of Prl On Kisspeptin Expression and Lh Secretion In Lsupporting

confidence: 81%

“…Indeed, kisspeptin neurons of these murine species seem to be endowed with distinct regulatory properties. For instance, high numbers of kisspeptin-ir neurons are present in the AVPV of the female mouse, whereas in the rat, kisspeptin-ir neurons can be properly found only after axonal transport inhibition (51). Alternatively, oPRL may have been ineffective in decreasing kisspeptin expression in the AVPV of OVX rats, because kisspeptin levels were already at basal levels due to the lack of E2 stimulation.…”

Section: Discussionmentioning

confidence: 99%

Prolactin Regulates Kisspeptin Neurons in the Arcuate Nucleus to Suppress LH Secretion in Female Rats

et al. 2014

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Prolactin (PRL) is known to suppress LH secretion. Kisspeptin neurons regulate LH secretion and express PRL receptors. We investigated whether PRL acts on kisspeptin neurons to suppress LH secretion in lactating (Lac) and virgin rats. Lac rats displayed high PRL secretion and reduced plasma LH and kisspeptin immunoreactivity in the arcuate nucleus (ARC). Bromocriptine-induced PRL blockade significantly increased ARC kisspeptin and plasma LH levels in Lac rats but did not restore them to the levels of non-Lac rats. Bromocriptine effects were prevented by the coadministration of ovine PRL (oPRL). Virgin ovariectomized (OVX) rats treated with either systemic or intracerebroventricular oPRL displayed reduction of kisspeptin expression in the ARC and plasma LH levels, and these effects were comparable with those of estradiol treatment in OVX rats. Conversely, estradiol-treated OVX rats displayed increased kisspeptin immunoreactivity in the anteroventral periventricular nucleus, whereas oPRL had no effect in this brain area. The expression of phosphorylated signal transducer and activator of transcription 5 was used to determine whether kisspeptin neurons in the ARC were responsive to PRL. Accordingly, intracerebroventricular oPRL induced expression of phosphorylated signal transducer and activator of transcription 5 in the great majority of ARC kisspeptin neurons in virgin and Lac rats. We provide here evidence that PRL acts on ARC neurons to inhibit kisspeptin expression in female rats. During lactation, PRL contributes to the inhibition of ARC kisspeptin. In OVX rats, high PRL levels suppress kisspeptin expression and reduce LH release. These findings suggest a pathway through which hyperprolactinemia may inhibit LH secretion and thereby cause infertility.

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Comparative analysis of kisspeptin-immunoreactivity reveals genuine differences in the hypothalamic Kiss1 systems between rats and mice

Cited by 44 publications

References 42 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

Rapid modulation of hypothalamic Kiss1 levels by the suckling stimulus in the lactating rat

Prolactin Regulates Kisspeptin Neurons in the Arcuate Nucleus to Suppress LH Secretion in Female Rats

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