Analysis of the disruption in hypothalamic-pituitary regulation in rats treated neonatally with monosodium L-Glutamate (MSG): Evidence for the involvement of tuberoinfundibular cholinergic and dopaminergic systems in neuroendocrine regulation

Charles B. Nemeroff, Richard J. Konkol, Garth Bissette, William Youngblood, Joseph B. Martin, Paul Brazeau, Michael S. Rone, George R. Breese, John S. Kizer

Research output: Contribution to journalArticlepeer-review

186 Scopus citations

Abstract

Adult rats which have received monosodium-L-glutamate (MSG) (4 mg/g body weight) on alternate days for the first ten days of life acquire neurotoxic lesions of the retina and arcuate nucleus and manifest an endocrine deficiency syndrome characterized by stunted growth, obesity, hypothyroidism, hypogonadism and pituitary atrophy. In the present study, the biochemical basis for the MSG-induced endocrine dysfunction has been examined and the findings of note are as follows: normal serum levels of TSH and LH despite hypothyroidism and gonadal atrophy, and significantly reduced serum GH levels in both males and females; elevated serum PRL levels in males, but not females; normal or augmented pituitary release of LH and TSH to exogenous LHRH and TRH. Within the central nervous system: a normal diurnal rhythm of pineal N-acetyltransferase activity despite optic atrophy; normal concentrations of LHRH, TRH and somatostatin within the medial basal hypothalamus; normal concentrations of norepinephrine (NE), choline acetyltransferase (CAT) and dopamine (DA) in all extrahypothalamic regions examined; normal concentrations of serotonin (5HT) and NE, but greatly reduced concentrations of DA (40-50%) and CAT activity (70-75%) in the arcuate nucleus (ARC) and median eminence (ME) of the hypothalamus. From these findings several conclusions were drawn: The MSG-induced endocrine deficiency syndrome appears to result from the destruction of ARC-ME dopaminergic and cholinergic tuberoinfundibular systems within the hypothalamus; a normal concentration of serotonergic and noradrenergic neurons within the hypothalamus does not insure normal central neuroendocrine regulation; no more than 50% of the dopaminergic terminals in the ME arise from ARC perikarya; cell bodies within the ARC contribute very few, if any, nerve terminals containing releasing factors to the ME; MSG destroys the primary optic tracts while sparing the retino-hypothalamic projection; LHRH, somatostatin and TRH are not contained within cholinergic nerve terminals in the ME.

Original languageEnglish (US)
Pages (from-to)613-622
Number of pages10
JournalEndocrinology
Volume101
Issue number2
DOIs
StatePublished - Aug 1977
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology

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