Effect of somatostatin-28 on growth hormone response to growth hormone-releasing hormone--impact of aging and lifelong dietary restriction.

The present study was designed to investigate the modulating effect of aging and lifelong dietary restriction (DR), a powerful anti-aging intervention in laboratory rodents, on growth hormone (GH) secretion from pituitary cells in response to GH-releasing hormone (GHRH) in the presence of somatostatin (SS)-28. Dispersed pituitary cells from 6- and 24-month-old rats fed ad libitum (AL-Y, AL-O, respectively) and 24-month-old rats dietary restricted from 6 weeks of age (DR-O) were subjected to a reverse hemolytic plaque assay under variable conditions including GHRH (0, 1, 10 nM) and SS-28 (0, 10 nM). The proportion of GH plaque-forming cells in dispersed pituitary cells increased by GHRH and decreased by SS-28. The proportion of these cells was lowest in AL-O rats; it was lower in DR-O than in AL-Y rats, particularly in the presence of SS-28. The reduction in these cells by SS-28 was greatest in Group AL-O. The mean area of these plaques, reflecting the amount of GH released from individual cells, was not different among the three rat groups in the absence of SS-28. In contrast, SS-28 produced a significantly higher reduction in the plaque area in Group AL-O compared with AL-Y and DR-O rats. Our results indicated that: (1) aging did not alter the responsiveness of GH-secreting cells to GHRH for GH secretion, while increased sensitivity of GH-secreting cells to SS-28 was noted in aged rats; (2) lifelong dietary restriction did not modulate the responsiveness to GHRH but partially inhibited the age-related increase in the sensitivity to SS-28 of GH-secreting cells, and (3) the major impact of the dietary regimen may include modulation of the number of pituitary cells, which leads to a high proportion of GH-secreting cells compared with that in AL rats at the same chronological age.