ALTERATIONS OF PITUITARY GROWTH HORMONE-RELEASING FACTOR BINDING SITES IN AGING RATS

Abstract

This study was designed to determine whether growth hormone (GH)-releasing factor (GRF) binding sites are altered in parallel to the diminution of GH secretion that occurs in aging. Using [125I-Tyr10] hGRF (1-44)NH2 as radioligand, we performed cold saturation studies in 2, 8, 14 and 18-month-old Sprague-Dawley male rat pituitary homogenates. In young rats (2 months), analysis by Ligand revealed the presence of two distinct classes of binding sites (KDs = 0.86 +/- 0.15 and 400 +/- 210 nM; BMAXS = 269 +/- 47 fmol and 42 +/- 19 pmol/mg protein, respectively). In 8 and 14-month old rats, there was a concomitant decrease in capacity of the high affinity class of sites (P less than 0.01) and increase in capacity of the low affinity class of sites (P less than 0.05). In parallel, a transient increase in affinity of the high affinity class of sites was observed in 14-month-old rats (P less than 0.05). In old rats (18 months), the data were no longer statistically analyzed with a two site-model, indicating a severe blunting of the high affinity sites. As the GRF-induced GH secretion is still not diminished at 8 month of age in these animals, our results indicate: 1) that alterations of GRF binding sites precede the GH impairment, thus probably participate in the initiating of this phenomenon and 2) that the biological actions of GRF on GH secretion are likely mediated by the high affinity class of sites.