Growth hormone-releasing factor (GRF) regulates expression of its own receptor

Recent studies have demonstrated that passive immunization of neonatal rats to GRF inhibited their somatic growth through the suppression of GH secretion. In this study, we investigated the changes in pituitary GRF receptor (GRFR) expression in GRF antibody (GRF-ab) treated rats. Neonatal rats were treated from day 1 to day 10 after birth with every other day sc injection of 50 microliters of normal rabbit serum (groups I: control & III) or rabbit serum containing GRF-ab (groups II & IV). In addition, groups III & IV received twice daily injection of recombinant human GH (0.4 microgram/kg, sc). The rats were sacrificed on day 11 and pituitaries were removed. The pituitary weights in all treatment groups were decreased compared to the control group (I). Total pituitary RNA was extracted and GRFR mRNA levels were determined by RNase protection assay. Receptor RNA levels were quantitated and normalized to an internal standard, glyceraldehyde 3-phosphate dehydrogenase (GAPDH). The ratios of GRFR mRNA to GAPDH mRNA were significantly decreased to 49.6 +/- 4.9 (mean +/- SD), 73.0 +/- 8.7, 43.6 +/- 9.5% of control group I in the experimental groups II, III, and IV, respectively (P < 0.01). These data suggest that (1) suppression of GH secretion in GRF-ab treated animals was due, at least in part, to a decrease in GRFR expression, (2) GRF may be necessary for its own receptor expression, (3) exogenous administration of GH suppresses pituitary GRFR mRNA.