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

Abstract

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.

Kisspeptin system in ovariectomized mice: Estradiol and progesterone regulation

“…3b). However as demonstrated in our previous study, the distribution of PVN kiss-ir fibers is not homogeneous in PVN comparing the medial with the lateral part of the nucleus (Marraudino et al, 2017).…”

“…Therefore, sex steroids indirectly regulate GnRH neurons and the mediator is Kisspeptin, whose neurons express estrogen receptor alpha, ERα ( 90%; Franceschini et al, 2006;Smith et al, 2005), AR ( 65%; Smith et al, 2005), and the progesterone receptor ( 86%; Smith et al, 2007). In rodents, sex steroids differentially regulate Kisspeptin expression in hypothalamus, which increases in the RP3V region (Kauffman et al, 2007;Smith et al, 2005) and PVN (Marraudino et al, 2017), and decreases in the ARC (Smith et al, 2005).…”

“…Therefore, the presence of kisspeptin fibres in the PVN may represent a link among the control of metabolism and reproduction. In a previous study we demonstrated that the innervation of the PVN shows regional differences (medial versus lateral, dorsal versus ventral) and also it changes in estrus and diestrus suggesting that it derives predominantly from RP3V, but not excluding a component arising from the ARC (Marraudino et al, 2017).…”

“…In addition to the GnRH system, one of the major hypothalamic targets of the kisspeptin system is the paraventricular hypothalamic nucleus (PVN) (Marraudino et al, 2017). The PVN is one of the most important autonomic control centres in the brain, and its neurons, organized into subdivisions, play essential roles in controlling several endocrine and autonomic functions including metabolism (for a review see Ferguson et al, 2008).…”

Exposure of female mice to perfluorooctanoic acid suppresses hypothalamic kisspeptin‐reproductive endocrine system through enhanced hepatic fibroblast growth factor 21 synthesis, leading to ovulation failure and prolonged dioestrus

“…For frozen sections, the brains were gradually transferred into 15% and 30% sucrose. After the brains completely sank to the bottom in 30% sucrose, coronal sections (30 μm) through the AVPV (from bregma +0.62 to +0.02 mm) 28 and ARC (from bregma −1.22 to −2.80 mm) 34,35 were serially cut using a cryostat (Leica Microsystems, Wetzlar, Germany). All free‐floating sections through the AVPV and ARC were collected and incubated in 0.5% sodium metaperiodate for 20 minutes and then in 1% sodium borohydride for 20 minutes.…”