Abstract

N-methyl-D-aspartate (NMDA), a specific agonist of the NMDA-type glutamate receptor, has been shown to stimulate the release of several anterior pituitary hormones when administered in vivo. The primary site of action of NMDA has been suggested to be at the level of the hypothalamus via the control of hypothalamic releasing factors. However, recent studies have demonstrated that NMDA can exert stimulatory effects directly upon anterior pituitary cells perifused in vitro, suggesting that the anterior pituitary may also be a site of action for glutamate. Hence, the purpose of the present study was to determine whether the NMDA R(1) receptor subunit is co-localized in specific hormone-secreting cells of the anterior pituitary. To achieve this aim, immunohistochemical studies were performed using an antibody specific for the NMDA R(1) receptor subunit to stain sections from the pituitaries of steroid-treated ovariectomized immature rats. Double-immunohistochemistry was employed to demonstrate co-localization, The results of the studies revealed that moderate immunoreactive NMDA R(1) receptor staining was observed in the anterior and intermediate lobe of the pituitary with little staining observed in the posterior lobe. Double-immunohistochemistry using antibodies for the NMDA R(1) receptor subunit and specific anterior pituitary hormones revealed that the NMDA R(1) receptor subunit is co-localized in many cell types of the anterior pituitary including LH (11.2%), FSH (9%), GH (4.6%), TSH (5.7%) and PRL cells (8%). Only one ACTH cell was found to co-localize the NMDA R(1) receptor subunit. Finally, Northern blot analysis revealed that the anterior pituitary of the adult female rat, like the immature rat, possesses NMDA R(1) receptor subunit mRNA. Taken as a whole, the present study provides further evidence that, in addition to the hypothalamus, the anterior pituitary could be an important site of action for the neuroendocrine effects of excitatory amino acids.