title: Characterization and ontogenesis of N-methyl-d-aspartate-evoked luteinizing hormone secretion in immature female rats.
abstract: The excitatory amino-acid L-glutamate appears to be involved in the neural regulation of puberty. We have now characterized the stimulatory effect of the glutamate agonist N-methyl-D-aspartic acid (NMDA) on the secretion of luteinizing hormone (LH) in immature female rats. NMDA injections (subcutaneously) rapidly induce LH secretion (maximum at 8 min) with an ED(50) of 3.25 mg/kg determined at postnatal day 30. The LH response to NMDA develops between 10 and 15 days after birth, reaches a maximum at approximately day 27 and disappears again by day 32, an age at which 80% of the rats are still prepubertal. In confirmation of work by others, we also showed that postpubertal male rats are unresponsive to NMDA. The effect of NMDA on LH release is blocked by prior injection of the glutamate antagonist MK-801 (0.1 mg/kg). MK-801 alone is able to reduce LH secretion in acutely ovariectomized rats but has little effect in intact, prepubertal rats. NMDA may not act exclusively on the gonadotropin-releasing hormone neuron since inhibition of norepinephrine biosynthesis by the drug U-14,624 largely prevents NMDA-induced LH secretion. Interestingly, rats treated neonatally with the neurotoxin monosodium glutamate responded normally to NMDA when tested at postnatal day 25. Finally, removal of the ovaries 48 h previously reduced the LH response to NMDA. Full responsiveness was restored following estrogen priming. In summary, hypothalamic glutamate receptors of the NMDA subtype comprise a significant regulatory component of LH secretion in prepubertal female rats. LH responsiveness appears to be age-, dose-, estrogen- and norepinephrine-dependent.
authors.affiliation: Department of Obstetrics and Gynaecology, School of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7. Department of Physiology and Biophysics, School of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7.
authors.forename: M C
authors.initials: MC
authors.lastname: Macdonald
authors.forename: M
authors.initials: M
authors.lastname: Wilkinson