Increased secretion of somatostatin-28 from hypothalamic neurons of aged rats in vitro

The purpose of this experiment was to determine whether increased secretion of somatostatin or alterations in its molecular form contribute to the age-related decline in growth hormone secretion. Median eminences were removed from male Sprague-Dawley rats (3-4 and 21-24 months of age) and superfused with Krebs-Ringer bicarbonate buffer with 0.5 mg/ml bacitracin. After 40 min, tissues were stimulated with 55 mM K+ for 5 min and fractions collected for 60 min. Tissue and superfusate were analyzed for somatostatin using a highly specific antiserum which cross-reacts with somatostatin-14 and -28. Somatostatin release was expressed as a fractional efflux of somatostatin tissue content. In young rats, somatostatin increased from basal levels of 22 +/- 5 X 10(-4) to 57 +/- 3 X 10(-4) in response to 55 mM K+ and returned to basal levels. Old rats exhibited similar basal levels of somatostatin efflux (25 +/- 5 X 10(-4)) but increased to 91 +/- 19 X 10(-4) in response to K+. This represents an 89% greater increase in somatostatin fractional efflux in old as compared to young rats (P less than 0.05). The molecular form of somatostatin released during K+ stimulation was determined by fractionating samples on Sephadex G-25. In young animals, both somatostatin-14 (31% of total immunoreactivity) and somatostatin-28 (69% of total immunoreactivity) were released by hypothalamic neurons. In old rats, similar absolute levels of somatostatin were released in response to K+ but greater quantities of somatostatin-28 (87% of total immunoreactivity) were secreted.(ABSTRACT TRUNCATED AT 250 WORDS)