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Increase in mRNA Concentrations of Pituitary Receptors for Growth Hormone‐Releasing Hormone and Growth Hormone Secretagogues After Neonatal Monosodium Glutamate Treatment
Author(s) -
Magdolna Kovàcs,
Rhonda D Kineman,
Andrew V. Schally,
Béla Flerkó,
Lawrence A. Frohman
Publication year - 2000
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1046/j.1365-2826.2000.00458.x
Subject(s) - medicine , endocrinology , monosodium glutamate , receptor , growth hormone–releasing hormone , hypothalamus , pituitary gland , anterior pituitary , ghrelin , hormone , secretagogue , chemistry , biology , growth hormone
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.