Session: FP04-GnRH & Gonadotroph Biology & Signaling
Room 135 (Moscone Center)
Poster Board SAT-137
We studied the role of rbcn3-α in pubertal onset by producing Dmxl2-knock-out mice. Our results revealed no significant phenotype in heterozygous (HET) Dmxl2 hypomorphic mice, which are fertile. We hypothesized that mice with both HET hypomorphic and neuronally deleted Dmxl2 (Dmxl2/Nes-Cre) would display worsened parameters of puberty. Indeed, Dmxl2/Nes-Cre HET mice are infertile. Dmxl2/Nes-Cre HET female mice had a significant delay in puberty associated with few ovulations, confirmed by low numbers of corpus lutea. HET male Dmxl2/Nes-Cre mice had significantly shorter anogenital distance and undetectable testosterone levels. Important, we observed that rbcn3-α is co-localized with synaptophysin and vesicular glutamate transporter (VGLUT)-2 in the ME and is involved in vesicle exocytosis.
Our results reveal that rbcn3-α plays a key role in puberty in both humans and mice. These studies expose a novel mechanism in the activation of the HPG axis whereby rbcn3-α is a synaptic protein that could modulate glutamate, KP, and/or GnRH release in the ME. Rbcn3-α may be one major protein controlling the plasticity of the neuroendocrine network regulating GnRH release. As patients with a Dmxl2 deficiency have been discovered, these data are of great clinical relevance, allowing a deeper understanding of the reactivation of the HPG axis at puberty.
Nothing to Disclose: BKT, JL, LH, SJ, JCC, ND
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