Pituitary Growth Hormone-Releasing Factor Receptor Expression in Normal and Dwarf Rats

Growth hormone-releasing factor (GRF) regulates GH release and somatotrope proliferation via a specific G-protein-coupled receptor. Little is known about the endocrine factors that regulate the expression of the GRF receptor (GRF-R) in the pituitary gland. We have developed a sensitive solution hybridization/RNAse protection assay for GRF-R mRNA in rat pituitary extracts. GRF-R transcripts were readily detectable in similar amounts in normal male and female rats, but were markedly reduced in extracts from age-matched growth hormone (GH)-deficient dwarf (dw) rats of either sex. The reduced GRF-R expression would appear to reflect somatotrope hypoplasia rather than GH deficiency per se since a similar reduction in GRF-R expression was seen in a transgenic model of dominant dwarfism, whereas GRF-R expression was significantly elevated in rats with GH deficiency induced by hypothyroidism. We were unable to demonstrate significant effects on GRF-R expression with infusions of human GH (hGH) or insulin-like growth factor 1, which stimulate growth in dw rats, but dexamethasone treatment induced a significant, time-related increase in GRF-R mRNA levels. We conclude that this assay can usefully quantify pituitary GRF-R expression in normal rats, and its reduction in two different strains of mutant dwarf rats with somatotrope hypoplasia.