Effects of Neurotoxic Excitatory Amino Acids on Neuroendocrine Regulation

Abstract

This report surnmarizes the available literature concerning the effects of glutamate and related excitatory amino acids on neuroendocrine function. The majority of investigators in this field have pursued two lines of inquiry: (1) evaluation of the effect of administration of monosodium glutamate (MSG) and related excitotoxic amino acids to neonatal rodents on endocrine regulation in adulthood and (2) assessment of the acute neuroendocrine effects of MSG and related compounds in adult rodents. The use of these compounds as tools in neuroendocrine research is described. KEYWORDSMonosodium glutamate (MSG); n-methyl aspartate (NMA); growth hormone (GH); prolactin (PRL); luteinizing hormone (LH).; follicle-stimulating hormone (FSH); thyrotropin (TSH); hypothalamic releasing hormones; dopamine; acetylcholine.

Peripubertal Treatment with N-Methyl-D-Aspartic Acid or Neonatally with Monosodium Glutamate Accelerates Sexual Maturation in Female Rats, an Effect Reversed by MK-801

“…However, estradiol target neurons are also eliminated by MSG [14], and dopamine [20], |)-endorphin [1] and GABA [14] concentrations are all severely reduced in MSG-treated rats. These neural defi cits are accompanied by profound endocrine abnormalities [20,24]. Our use of lower doses of MSG ( x 2 injections; 4 mg/g body weight), in agreement with Dawson [9], had little influence on normal prepubertal growth.…”

“…|)-endorphin) and yaminobutyric acid (GABA), are thought to negatively control gonadotropin secretion [5,17,29], Neurons which contain nor epinephrine, serotonin and GnRH are spared [14]. However, estradiol target neurons are also eliminated by MSG [14], and dopamine [20], |)-endorphin [1] and GABA [14] concentrations are all severely reduced in MSG-treated rats. These neural defi cits are accompanied by profound endocrine abnormalities [20,24].…”

“…Neonatal injections of MSG were based upon extensive published data (20,24], In an attempt to reduce the mortality rate we elected to inject MSG (4 mg/g, s.c.) on days 2, 4, 6 and 8 of life. The majority of pups survived this treatment.…”

“…Monosodium glutamate (MSG), when injected neonatally, is a neurotoxin which destroys neurons in the ar cuate nucleus. Thus, neurons which possess glutamate recep tors are eliminated [20,31). We have, therefore, examined whether neonatal MSG treatment influences the timing of pu berty.…”

Effects of Intrahypothalamic Injection of Quinolinic Acid on Anterior Pituitary Hormone Secretion in the Unanesthetized Rat

“…All QUIN-induced hormonal changes were inhibited by concomitant administration of the specific antagonist (-)-2-amino-7-phosphonoheptanoic acid, indicating the presence of QUIN-sensitive receptors on neurons which are intimately associated with endo crine regulation. Moreover, because QUIN-treated animals exhibited behavioral signs of seizure activity and neuroendo crine dysfunction has been reported to occur in human convulsive disorders, the data are also of interest in view of a possible mechanistic link between epileptic phenomena and hormone secretion.The effects of systemically administered excitatory ami no acids on anterior pituitary hormone secretion in the rat have been studied, and these data have been reviewed [13]. Subcutaneous administration of monosodium I-glutamate (MSG) to adult male rats was originally reported to pro duce a rapid rise in the serum concentrations of luteinizing hormone (LH) and testosterone [17].…”