Elsevier

Brain Research

Volume 184, Issue 2, 24 February 1980, Pages 425-437
Brain Research

Acute central stimulation of luteinizing hormone by parenterally administeredN-methyl-D, L-aspartic acid in the male rat

https://doi.org/10.1016/0006-8993(80)90810-0Get rights and content

Abstract

N-methyl-d,l-aspartic acid (NMA), a potent neuroexcitatory and neurotoxic glutamic acid analogue, acutely elevates serum luteinizing hormone (LH) in male rats when given subcutaneously in doses below those that cause morphologically detectable hypothalamic neurotoxicity. NMA treatment in doses known to be subtoxic by morphological criteria fails to induce any permanent neuroendocrine dysfunction as assessed by several physiological parameters, including NMA responsiveness after multiple consecutive doses spaced at 24 h intervals, subsequent basal LH levels and subsequent postcastration LH elevations. Like naloxone, NMA elevates serum LH by reversibly stimulating a central labile pool. Neither has a direct stimulatory effect on the pituitary in vitro. Treatment with either attenuates naloxone-induced LH stimulation 2 h, but not 14 days, later while pituitary responsiveness to LHRH in vivo remains unaltered. Neither NMA nor naloxone is dependent upon testosterone for its LH stimulatory action and both increase serum LH through physiological mechanisms responsive to testosterone inhibition. It is concluded that subtoxic LH stimulating doses of NMA provide a useful tool in discerning neurotransmitter systems involved in central control of the hypothalamic-pituitary-gonadal axis.

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      This amino acid is implicated in the stimulation of a class of glutamate receptors, some of which are also involved in learning and memory [1–6]. Furthermore, NMDA has been demonstrated to be involved in the regulation of the release and synthesis of gonadotropin releasing hormone from the hypothalamus [7–9] and luteinizing hormone [8,10–15], prolactin [12–14], and growth hormone from the pituitary gland [15–17]. In our previous work we reported for the first time the presence of NMDA in rat neuroendocrine tissues [20].

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