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

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 grow th 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 a ltered in this model of GHRH deficiency. In addition, we investigated if tr eatment 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 pre vious 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 main tenance of a normal GH concentration, GH mRNA concentration (per mu g 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 reduct ion in the GH secretory rate, acts to maintain intracellular GH concentrati ons. The fall in circulating concentrations of GH leads to a 42% decrease i n 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 mu g 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 lev els, 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 G H secretion and GH in turn stimulates hepatic IGF-I but that effects on gen e expression are not sustained. Collectively, our observations demonstrate. a complex interplay between transcriptional, translational and post-transl ational mechanisms within each level of the GH-axis following destruction o f GHRH neurones by neonatal MSG treatment.