Increase in mRNA concentrations of pituitary receptors for growth hormone-releasing hormone and growth hormone secretagogues after neonatal monosodium glutamate treatment

Magdolna Kovacs, R. D. Kineman, Andrew V Schally, B. Flerko, L. A. Frohman

Research output: Contribution to journalArticle

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Abstract

Previous studies have demonstrated that neonatal monosodium glutamate (MSG) treatment destroys growth hormone releasing-hormone (GHRH) neurones within the hypothalamic arcuate nucleus, decreases serum GH and insulin-like growth factor (IGF-I) concentrations, and retards linear growth. In the present study we investigated whether expression of pituitary GH, GHRH receptors (GHRH-R), growth hormone secretagogue receptors (GHS-R) and liver IGF-I is altered in this model of GHRH deficiency. In addition, we investigated if treatment of MSG-lesioned rats with the GHRH agonist, JI-38, would 'normalise' the GH-axis. Serum GH and IGF-I concentrations were determined by RIA, GH mRNA levels were evaluated by Northern blotting, and GHRH-R, GHS-R and IGF-I mRNA levels were measured by semiquantitative RT-PCR. In accord with previous reports, neonatal MSG treatment caused 50% and 76% decreases in serum GH and IGF-I concentrations, respectively, at 8 weeks of age. The decline in circulating GH was accompanied by a 56% reduction in total pituitary GH content, which was a reflection of the decrease in total pituitary protein. However, GH concentration (per mg protein) was unaltered. Despite the maintenance of a normal GH concentration, GH mRNA concentration (per μg total RNA) was suppressed by 42%, compared to saline-treated controls (P < 0.05). These data indicate that a post-transcriptional mechanism, such as a reduction in the GH secretory rate, acts to maintain intracellular GH concentrations. The fall in circulating concentrations of GH leads to a 42% decrease in liver IGF-IB mRNA levels, while liver IGF-IA transcripts showed only a 27% suppression. In contrast, pituitary GHRH-R and GHS-R mRNA levels (per μg total RNA) were increased in MSG-lesioned rats by 96% and 180% of normal values (P < 0.01), respectively. Twice daily treatment of MSG-lesioned rats (for 2 weeks) with the GHRH agonist, JI-38, increased serum GH and IGF-I levels, as measured 20 h after the last agonist injection. However, GH, IGF-I, GHRH-R and GHS-R mRNA levels were not altered at this time. These results demonstrate that intermittent GHRH agonist treatment stimulates pituitary GH secretion and GH in turn stimulates hepatic IGF-I but that effects on gene expression are not sustained. Collectively, our observations demonstrate a complex interplay between transcriptional, translational and post-translational mechanisms within each level of the GH-axis following destruction of GHRH neurones by neonatal MSG treatment.

Original languageEnglish
Pages (from-to)335-341
Number of pages7
JournalJournal of Neuroendocrinology
Volume12
Issue number4
DOIs
StatePublished - Mar 29 2000
Externally publishedYes

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Growth Hormone-Releasing Hormone
Sodium Glutamate
Insulin-Like Growth Factor I
Growth Hormone
Ghrelin Receptor
Messenger RNA
Liver
Serum
Secretory Rate
RNA
Pituitary Hormone-Releasing Hormones
Neurons
Arcuate Nucleus of Hypothalamus
Therapeutics
Northern Blotting
Reference Values
Proteins
Maintenance
Gene Expression
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)

Cite this

Increase in mRNA concentrations of pituitary receptors for growth hormone-releasing hormone and growth hormone secretagogues after neonatal monosodium glutamate treatment. / Kovacs, Magdolna; Kineman, R. D.; Schally, Andrew V; Flerko, B.; Frohman, L. A.

In: Journal of Neuroendocrinology, Vol. 12, No. 4, 29.03.2000, p. 335-341.

Research output: Contribution to journalArticle

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