EXPRESSION OF ESTROGEN AND PROGESTERONE RECEPTORS IN GLUTAMATE AND GABA NEURONS OF THE PUBERTAL FEMALE MONKEY HYPOTHALAMUS

We have previously reported direct glutamate (Glu) synapses upon GnRH- containing neurons in the primate hypothalamus, and extensive interact ions between Glu and aminobutyric acid (GABA) neurons in areas associa ted with reproductive function. Both Glu and GABA are known to affect peripubertal GnRH neurohormone release, but their relative roles remai n unclear. In a developmental survey, estrogen receptors (ER) and prog esterone receptors (PR) were virtually undetectable after immunostaini ng the hypothalamus of prepubertal monkeys, but were clearly evident i n neurons of adults. We hypothesized, therefore, that Glu and GABA neu rons which develop ER or PR expression during puberty may participate in reactivation of the hypothalamic-pituitary-gonadal axis. To identif y those neurons in midpubertal female cynomolgus monkeys, we performed immunofluorescence staining for ER or for PR in separate sets of hypo thalamic sections, and then immunostained for Glu or for glutamate dec arboxylase (GAD, to identify GABA neurons) using a contrasting fluorop hore. ER and PR were localized in the cytoplasm and nuclei of Glu and GAD neurons in nine hypothalamic and related brain regions. Quantitati on revealed intranuclear ER in an average of 80% of the Glu neurons in all regions analyzed, and an average of 84% of the GAD neurons in all regions except the supraoptic nucleus (28%). Intranuclear PR expressi on was more variable, occurring in an average of 93% of the Glu neuron s in seven regions, but in only 41% in the medial preoptic area, and 0 % in the arcuate-periventicular zone. In addition, while intranuclear PR was seen in 96% of the GAD neurons in the septum, it appeared in 67 % of the GAD neurons in the paraventricular nucleus, 47% in the medial preoptic area, 40% in the periventricular zone, and was absent from n eurons in the supraoptic nucleus and mammillary bodies. In summary, ce rtain subpopulations of Glu and GABA neurons in principal hypothalamic regions of the female monkey express ER and PR at midpuberty. Taken t ogether with previous findings, these results suggest that Glu and GAB A neurons which become sensitive to steroid hormones may help regulate GnRH neurohormone release and promote the onset of puberty. Since neu ronal expression of ER or PR connotes sensitivity to gonadal feedback, and intranuclear translocation signals transcriptional activation, th ese results provide insights into the specific neuronal events involve d in the peripubertal transition in primates.