A Physiological Role for N-Methyl-D-Aspartic Acid and Non-N-Methyl-D-Aspartic Acid Receptors in Pulsatile Gonadotropin Secretion in the Adult Female Rat

The present study was designed to evaluate the physiological role of excitatory amino acids (EAAs) in the pulsatile secretion of LH and FSH. Specific antagonists for N-methyl-D-aspartic acid (NMDA) receptors and kainate/quisqualate (non-NMDA) receptors were used to achieve this aim. Adult female rats (250-280 g), ovariectomized for 2 weeks, were implanted with a cannula in the third ventricle of the brain. One week later, 2-amino-5-phosphono-pentanoic acid (AP-5; 10 μg/rat), a specific competitive NMDA receptor antagonist; 6,7-dinitroquinoxaline-2,3-dione (DNQX; 30 nM), a selective antagonist of non-NMDA receptors; or the same volume of saline, was injected via the third ventricle to conscious and unrestrained ovariectomized animals. Blood samples were collected from indwelling jugular catheters 20 min before and after injection and at 10-min intervals for 100 min for plasma LH and FSH determinations. The results revealed that the administration of either AP-5 or DNQX significantly suppressed mean as well as trough LH levels. This suppression was accompanied by a suppression of LH pulse frequency and LH pulse amplitude. AP-5 suppressed LH pulse amplitude, trough LH levels, and mean LH levels to a greater degree than DNQX. The analysis of FSH pulses showed that AP-5 inhibited mean and trough FSH levels, and this appeared to be achieved by the suppression of FSH pulse amplitude, but not frequency. DNQX, on the other hand, did not significantly alter FSH pulse frequency, pulse amplitude, or trough or mean FSH levels. Taken as a whole, the present study provides evidence that endogenous EAAs, acting through both NMDA and non-NMDA receptors, play an important physiological role in the generation of pulsatile LH secretion in adult female rats. FSH pulse frequency was not significantly affected by the administration of either EAA receptor antagonist, although AP-5 did suppress FSH pulse amplitude and mean and trough FSH levels.