Identification of Neurones in the Female Rat Hypothalamus That Express Oestrogen Receptor‐Alpha and Vesicular Glutamate Transporter‐2

Abstract

Oestrogen exerts its effects in the brain by binding to and activating two members of the nuclear receptor family, oestrogen receptor (ER)-alpha and ER-beta. Evidence suggests that oestrogen-receptive neurones participate in the generation of reproductive behaviours and that they convey the oestrogen message to gonadotropin-releasing hormone (GnRH) neurones. The aim of the present study was to identify the neurochemical phenotype of a subset of oestrogen receptor-expressing neurones. To this aim, we focused on the glutamate neuronal system, which is one of the most important stimulators of GnRH synthesis and release. We used the presence of vesicular glutamate transporter-2 (VGLUT2) mRNA as a specific marker to identify glutamate neurones and employed dual in situ hybridization to localize ERalpha mRNA-(35S-labelling) and VGLUT2 mRNA-(digoxigenin-labelling) expressing neurones within the hypothalamus. The results show that the overall distribution of VGLUT2 mRNA and ERalpha mRNA are consistent with previous data in the literature. Dual-labelled neurones were localized in the ventrolateral part of the ventromedial nucleus where 81.3 +/- 3.4% of the ERalpha mRNA containing neurones expressed VGLUT2 mRNA, in the anteroventral periventricular nucleus (30% colocalization) and in the medial preoptic nucleus (19% colocalization). Only 4.4% of the ERalpha expressing neurones in the arcuate nucleus contained VGLUT2 mRNA. These findings reveal that certain subpopulations of oestrogen-receptive neurones are glutamatergic in select hypothalamic areas that are known to regulate reproductive behaviour and GnRH neurones in the female rat. Thus, the oestrogen signal could be propagated through glutamate neurones to distant sites and influence the activity of the postsynaptic neurones.

Dual-Phenotype GABA/Glutamate Neurons in Adult Preoptic Area: Sexual Dimorphism and Function

“…Furthermore, GABAergic neurons in the AVPV, but not those surrounding GnRH neurons in the rPOA, exhibit changes in GAD67 gene expression that parallel GABA release on the day of LH surge release (Curran-Rauhut and Petersen, 2002). Consistent with these findings, GABA and glutamate terminals provide most of the synaptic input to GnRH neurons (Herbison, 1998;Kiss et al, 2003;Lin et al, 2003;Petersen et al, 2003;Eyigor et al, 2004;Han et al, 2004), and receptors for GABA and glutamate are among the few types found on GnRH neurons (Petersen et al, 2003). Moreover, agonists or antagonists to these receptors disrupt E 2 -dependent LH surge release (Herbison and Dyer, 1991;Donoso et al, 1994;Brann and Mahesh, 1995).…”

“…First, glutamatergic (Eyigor et al, 2004) and GABAergic (Flugge et al, 1985) neurons in the AVPV contain ER. Furthermore, GABAergic neurons in the AVPV, but not those surrounding GnRH neurons in the rPOA, exhibit changes in GAD67 gene expression that parallel GABA release on the day of LH surge release (Curran-Rauhut and Petersen, 2002).…”

GABARAPL1 (GEC1): Original or copycat?

“…Indeed, estrogen receptors are highly expressed in the hypothalamus 21,29 and play a major role in the regulation of the reproductive axis through their control on the release of luteinizing hormone and follicle-stimulating hormone at the anterior pituitary. Moreover, the primary neurotransmitter inputs to these neurons are GABA A and glutamate, which exert their effects in the neurons through GABA A receptors GABARAPL1 (Structural Genomic Consortium, code: 2R2Q) are also highly similar.…”

“…The guinea-pig Gabarapl1 gene has a full-length ERE sequence (estrogen responsive element, reviewed in ref. 21) that is located in the first exon and described as the primary response element necessary for gene activation by Estradiol-17β (E 2 ) via ERα (estrogen receptor α).…”

Role of Kisspeptine in Regulation of Reproductive Function

“…если ГнРГ-нейроны сами экспрессируют ER, очевидно, что регулирующее действие эстра-диола на ГнРГ-нейроны может быть трансси-наптическим потому, что эстрадиол регулиру-ет синаптическую передачу к этим клеткам [44] и нейроны, которые считаются афферентными к ГнРГ-нейронам, экспрессируют как ER-α, так и ER-β [45][46][47][48]. Особый интерес вызывают последние ис-следования, посвященные нейромодулятору кисспептину, о возможности действия эстра-диола по механизму обратной связи при регу-ляции ГнРГ-нейронов [9,49,50].…”