Impaired ability of old male rats to secrete growth hormone in vivo but not in vitro in response to hpGRF(1-44).

The capacity of hpGRF (1-44) to induce release of GH in young (3-4 month old) versus old (19-21 month old) male rats was compared in vivo and in vitro. Injection of 1 ug/kg hpGRF to rats anesthetized with sodium pentobarbital increased plasma GH concentrations in young animals to greater than 1600 ng/ml within 5 min, and a dose of 10 ug/kg hpGRF increased GH levels to approximately 1900 ng/ml at 10 min. In old rats, plasma GH concentrations were increased after hpGRF but the increases were significantly lower than in the young rats at 5, 10, and 20 min after injection (P less than 0.01). The total GH released in old animals was calculated to be approximately 50% of that in young animals. In vitro release of GH from anterior pituitary slices incubated with hpGRF was also compared between young and old animals. After 20 min incubation with hpGRF (10(-9) or 10(-7) M) or vehicle, both young and old animals demonstrated a dose related and equivalent increase in GH release. These results indicate a reduced capacity of hpGRF to stimulate GH release in vivo in aged as compared to young male rats. This decline is believed to be due to a hypothalamic influence on the anterior pituitary since the in vitro response of anterior pituitary tissue to hpGRF was similar in young and old rats. The reduced response to hpGRF in old male rats in vivo may be due to increased release of or enhanced sensitivity to somatostatin.