Excitatory amino acids such as N-methyl-D,L-aspartic acid (NMDA) are thought to play an important role in the regulation of gonadotropin secretion. NMDA induces significant increases in plasma LH in a variety of animal models and these effects occur by activation of neural processes involved in excitation of LHRH neurons rather than by a direct action on the pituitary gland. We have taken advantage of this information to study the effects of NMDA on LH release and on changes in levels of LHRH mRNA in single neurons of adult rats treated neonatally with a high dosage of androgen. While iv NMDA evoked an increase in plasma LH in estrogen-treated ovariectomized control and androgen-sterilized rats (ASR), significantly less LH was released in ASR. LHRH mRNA levels in the organum vasculosum of the lamina terminalis (OVLT), the rostral (r), media (m) and caudal (c) preoptic (POA) regions were quantitated using in situ hybridization histochemistry and quantitative image analysis methods. LHRH mRNA levels in untreated controls and ASR did not differ in any of the brain regions examined. Within 1 h after NMDA, LHRH mRNA had increased significantly in OVLT and rPOA but not in mPOA and cPOA neurons of control rats and these mRNA levels remained elevated for 4 h. In contrast, NMDA treatment of ASR did not affect basal levels of LHRH mRNA in any region of the rostral hypothalamus. These observations suggest that neonatal androgen treatment of female rats either directly or indirectly affects the responsiveness of LHRH neurons to NMDA.(ABSTRACT TRUNCATED AT 250 WORDS)