Stimulating action of glutamate on GnRH expression and secretion is modulated by estradiol during gestation in the South American plains vizcacha (Lagostomus maximus).

DORFMAN VB, INSERRA PIF, CHARIF SE, SCHMIDT AR, CORTASA S, PROIETTO S, CORSO MC ; DI GIORGIO NP, LUX-LANTOS V; HALPERIN, JULIA; ALFREDO DANIEL VITULLO

Concon

Workshop; INTERNATIONAL WORKSHOP IN NEUROENDOCRINOLOGY (IWNE); 2017

IWNE

The South American plains vizcacha, Lagostomus maximus, shows reproductive features as massive poliovulation of up to 800 oocytes per cycle and ovulation at mid-gestation. We have described the localization of the gonadotropin-releasing hormone (GnRH) in neurons of the preoptic (POA) and supraoptic (SON) areas in female vizcachas. In addition, we showed that GnRH neurons express estrogen receptor alpha (ERa) and progesterone receptors (PR). Glutamate (GLU), is involved in the expression and delivery of GnRH, and its inputs on GnRH neurons are regulated by estradiol (E2) through specific receptors. The aim of this work was to study the involvement of E2 on glutamatergic systems and its relation on GnRH expression and secretion during gestation. Hypothalami of non-pregnant non-ovulating (NPNO), non-pregnant ovulating (NPO), early-pregnant (EP), mid-pregnant (MP), and term-pregnant (TP) female vizcachas (n=6 per group) were used to study GLU receptors (NMDA and GLUR5) expression by Western-blot, GnRH content by RIA, GnRH pulsatility under GLU modulation by RIA, and serum estradiol (E2) by ELISA. ANOVA followed by Newman-Keuls Multiple Comparisons test was used to determine significant differences among groups (p<0.05). Ovulating groups (NPO and MP), that showed significantly higher E2 values than non-ovulating groups (NPNO, EP and TP), depicted a significant increase in NMDA and GLUR5 expression pattern (p<0.05). This variations were concordant with GnRH expression and serum E2 levels throughout the reproductive cycle (p<0.05). To study the involvement of E2 on glutamatergic system, NPNO females were bilaterally ovariectomized (OVX) and after 5 days injected with E2 (1 mg/kg/day) during 5 days (OVX+E2). SHAM females injected with vehicle were used as controls (n=5 per group). NMDA expression was significantly increased in OVX+E2 vs. OVX and SHAM. To investigate GLU action on GnRH pulsatility, GnRH secretion was determined in hypothalamic explants incubated with GLU, GLU+NMDA antagonist, or GLU+GLUR5 antagonist (n=4 per group). GnRH pulsatility frequency was significantly increased by GLU vs. control, and by GLU+NMDA and GLU+GLUR5 antagonists related to control and GLU (p<0.05). These results suggest that the increase in the expression of GLU receptors at mid gestation could be induced by increments in E2 levels which would enable GnRH expression duringpregnancy (Fundación Científica Felipe Fiorellino, CONICET-PIP110/14, and MICyT-PICT1281/2014).