GONADAL-STEROIDS TARGET AMPA GLUTAMATE RECEPTOR-CONTAINING NEURONS INTHE RAT HYPOTHALAMUS, SEPTUM AND AMYGDALA - A MORPHOLOGICAL AND BIOCHEMICAL-STUDY

Interactions between glutamate and gonadal steroids are involved in th e regulation of limbic and hypothalamic functions. We hypothesized tha t hormonal signals affect excitatory neurotransmission by regulating t he expression of glutamate receptors (GluR) in limbic and hypothalamic regions. To test this hypothesis, first, the coexpression of ha-amino -3-hydroxy-5-methyl-4-isoxazone-propionate (AMPA) GluR1, GluR2/3, and androgen receptors or estrogen receptors was revealed in the same cell s of septal, amygdaloid, and hypothalamic areas by double immunocytoch emistry. The highest incidence of colocalization was detected in hypot halamic regions. To demonstrate a regulatory role of testosterone or e stradiol on AMPA receptor expression, the hormonal milieu of male and female rats was manipulated by gonadectomy and hormonal treatment. Glu R1 and GluR2/3 expression was assessed by Western blots. Statistical a nalysis demonstrated that testosterone and estradiol have a stimulator y influence on the expression of AMPA receptors in the hypothalamus. T he regulatory effect of estradiol on AMPA receptors was found to be si te and gender specific: after estradiol treatment, samples taken from the hypothalamus contained increased levels of GluR1 and GluR2/3, wher eas in the septum, bed nucleus and amygdala, no changes could be detec ted. Furthermore, the increase in hypothalamic GluR 2/3 levels was two times higher in females, compared with males, whereas the changes in hypothalamic GluR 1 levels showed no sex differences. Our results supp ort the hypothesis that the interaction between gonadal steroids and g lutamate involves hormone regulation of GluR. This mechanism seems to be gender and site specific, suggesting that excitatory neurotransmiss ion and related physiological mechanisms also may be distinctly differ ent in males and females.