The antero-ventral periventricular zone (AVPV) and medial preoptic area (MPOA) have
been recognized as gonadal hormone receptive regions of the rodent brain that-via
wiring to gonadotropin-releasing hormone (GnRH) neurons-contribute to orchestration
of the preovulatory GnRH surge. We hypothesized that neural genes regulating the induction
of GnRH surge show altered expression in proestrus. Therefore, we compared the expression
of 48 genes obtained from intact proestrous and metestrous mice, respectively, by
quantitative real-time PCR (qPCR) method. Differential expression of 24 genes reached
significance (p < 0.05). Genes upregulated in proestrus encoded neuropeptides (kisspeptin
(KP), galanin (GAL), neurotensin (NT), cholecystokinin (CCK)), hormone receptors (growth
hormone secretagogue receptor, mu-opioid receptor), gonadal steroid receptors (estrogen
receptor alpha (ERalpha), progesterone receptor (PR), androgen receptor (AR)), solute
carrier family proteins (vesicular glutamate transporter 2, vesicular monoamine transporter
2), proteins of transmitter synthesis (tyrosine hydroxylase (TH)) and transmitter
receptor subunit (AMPA4), and other proteins (uncoupling protein 2, nuclear receptor
related 1 protein). Proestrus evoked a marked downregulation of genes coding for adenosine
A2a receptor, vesicular gamma-aminobutyric acid (GABA) transporter, 4-aminobutyrate
aminotransferase, tachykinin precursor 1, NT receptor 3, arginine vasopressin receptor
1A, cannabinoid receptor 1, ephrin receptor A3 and aldehyde dehydrogenase 1 family,
member L1. Immunocytochemistry was used to visualize the proteins encoded by Kiss1,
Gal, Cck and Th genes in neuronal subsets of the AVPV/MPOA of the proestrous mice.
The results indicate that gene expression of the AVPV/MPOA is significantly modified
at late proestrus including genes that code for neuropeptides, gonadal steroid hormone
receptors and synaptic vesicle transporters. These events support cellular and neuronal
network requirements of the positive estradiol feedback action and contribute to preparation
of the GnRH neuron system for the pre-ovulatory surge release.