Paradoxical growth-promoting effects induced by patterned infusions of somatostatin in female rats.

In previous studies with iv infusions of GH or its releasing factor (GRF), we showed that a pulsatile pattern of GH was more effective than continuous GH exposure in stimulating growth in the rat. Since GH release is profoundly affected by its inhibitory factor, somatostatin (SS), we were interested to know whether the effects of SS on GH secretion and growth were also dependent on its pattern of administration. SS infusions were given iv to conscious chronically cannulated female rats through programmable multichannel infusion pumps. Multiple blood samples were obtained with the use of an automated system of pumps, solenoid fluid valves, and a fraction collector, all controlled by a microcomputer. SS infusions (5, 25, or 50 micrograms/h) suppressed GH secretion and elicited a rapid, short-lived rebound release of GH after stopping the infusion. Sinusoidal SS infusions in female rats produced cyclic episodes of GH secretion, but a male type of regular 3-hourly secretory pulses of GH was best achieved by prolonged infusions in which the delivery of SS was interrupted for a short period every 3 h. This intermittent SS infusion pattern elicited a repetitive series of rebound bursts of GH secretion, which increased body weight gain and pituitary GH content. In contrast, continuous infusions of equivalent amounts of SS had no effect on body weight gain and reduced bone growth significantly. Thus the effects of SS on growth do depend on the pattern in which it is administered, and this peptide, which itself powerfully inhibits GH secretion, paradoxically stimulates weight gain in a normal animal when given in a manner that promotes a more pulsatile GH secretory pattern.