STEROID-HORMONE EFFECTS ON NMDA RECEPTOR-BINDING AND NMDA RECEPTOR MESSENGER-RNA LEVELS IN THE HYPOTHALAMUS AND CEREBRAL-CORTEX OF THE ADULT-RAT

Previous work has demonstrated that N-methyl-D-aspartate (NMDA) is cap able of stimulating luteinizing hormone release in a variety of specie s. Interestingly, the ability of NMDA to stimulate luteinizing hormone release is significantly compromised in castrated male and female rat s as compared to intact animals. The purpose of the present study was to determine if a difference exists in the number or affinity of NMDA receptors in the hypothalamus of intact or castrated adult male and fe male rats and whether steroid replacement has any effect on NMDA recep tor binding. NMDA receptor mRNA levels were also determined in the res pective models. The cerebral cortex was used as a control to check for specificity of any observed differences. The number of NMDA binding s ites in the hypothalamus was found to be approximately 25% of that fou nd in the cerebral cortex and the equilibrium association constant was similar in both tissues. In the female rat, neither ovariectomy nor o variectomy with estrogen pellet replacement or estrogen and progestero ne injections altered NMDA receptor binding or the equilibrium associa tion constant in the hypothalamus or cerebral cortex as compared to in tact controls. Similar to the case in the female, NMDA receptor bindin g in the hypothalamus and cerebral cortex of male rats did not change after castration or after treatment with testosterone propionate. Neit her ovariectomy nor ovariectomy with estradiol replacement brought abo ut any change in the NMDA receptor mRNA levels in the hypothalamus. Ho wever, in the cerebral cortex ovariectomy with estrogen replacement br ought about a small but significant increase in NMDA receptor mRNA lev els. In summary, the results of the present study show that in the mal e and female rat, castration and steroid replacement do not alter NMDA receptor concentrations or affinity, nor NMDA receptor mRNA levels in the hypothalamus.