Kisspeptin innervation of the hypothalamic paraventricular nucleus: sexual dimorphism and effect of estrous cycle in female mice

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Journal of Anatomy , March 2017

Kisspeptin innervation of the hypothalamic paraventricular nucleus: sexual dimorphism and effect of estrous cycle in female mice

Marraudino M 1,2 , Miceli D 1,2 , Farinetti A 1,2 , Ponti G 3,2 , Panzica G 1,2 , Gotti S 1,2

The hypothalamic paraventricular nucleus (PVN) is the major autonomic output area of the hypothalamus and a critical regulatory center for energy homeostasis. The organism's energetic balance is very important for both the regular onset of puberty and regulation of fertility. Several studies have suggested a relationship among neural circuits controlling food intake, energy homeostasis and the kisspeptin peptide.

The kisspeptin system is clustered in two main groups of cell bodies [the anterior ventral periventricular region (AVPV) and the arcuate nucleus (ARC)] projecting mainly to gonadotropin-releasing hormone (GnRH) neurons and to a few other locations, including the PVN. In the present study, we investigated the distribution of the kisspeptin fibers within the PVN of adult CD1 mice. We observed a significant sexual dimorphism for AVPV and ARC, as well as for the PVN innervation.

Kisspeptin fibers showed a different density within the PVN, being denser in the medial part than in the lateral one; moreover, in female, the density changed, according to different phases of the estrous cycle (the highest density being in estrus phase). The presence of a profound effect of estrous cycle on the kisspeptin immunoreactivity in AVPV (with a higher signal in estrus) and ARC, and the strong co-localization between kisspeptin and NkB only in ARC and not in PVN suggested that the majority of the kisspeptin fibers found in the PVN might arise directly from AVPV.

1 Department of Neuroscience, Laboratory of Neuroendocrinology, University of Torino, Torino, Italy
2 Neuroscience Institute Cavalieri-Ottolenghi (NICO), Orbassano, Italy
3 Department of Veterinary Sciences, University of Torino, Grugliasco, Italy
Fig 1: Quantitative study of kisspeptin system in the hypothalamic nuclei. Histograms representing the fractional area covered by kisspeptin-immunoreactive (kiss-ir) structures (mean SEM) in the arcuate hypothalamic nucleus (ARC), anterior ventral periventricular nucleus (AVPV), periventricular nucleus (PeN) and paraventricular nucleus (PVN) of male (black bars) and female (white bars) CD1 mice. Males showed a lower immunoreactivity in comparison with the female group. **P < 0.01, ***P < 0.001 different from males (P < 0.05; Student’s t-test). Scale bar:100µm
Fig 2: Kisspeptin (Kiss) and paraventricular nucleus (PVN) cellular populations [arginine vasopressin (AVP), neural nitric oxide synthase (nNOS), oxytocin (OT), tyrosine hydroxylase (TH)]. Coronal section of the adult CD1 female mice PVN in estrus phase. It is possible to observe the relations with Kiss (red) and different PVN neuronal populations: ( A ) AVP (green); ( B ) nNOS (green); ( C ) OT (green); ( D ) TH (green). Note that the total AVP and the majority of nNOS neuronal cell bodies were distributed in lateral PVN, where the concentration of Kiss fibers was lower; in the medial PVN instead, a conspicuous number of OT and TH cell bodies were present. Scale bar: 50µm