A determinant factor in the efficacy of GHRH administration in promoting sleep: High peak concentration versus recurrent increasing slopes

A previous experiment indicated a greater efficacy of episodic than continuous growth hormone (GH)-releasing hormone (GHRH) administration in enhancing sleep. The greater efficacy of episodic administration could principally result from two factors, i.e. the greater peak concentration reached after episodic administration or the recurrence of increasing slopes in GHRH concentration. In order to investigate which factor essentially determines the pharmacodynamics of sleep promotion after GHRH, effects after a transient high peak in GHRH concentration were compared with those of repetitive increases in GHRH concentration. Sleep, plasma concentrations of GH, and GHRH were examined in healthy subjects after eyening administration of a 'single' IV bolus of 50 μg GHRH, after five 'repetitive' boluses of 10 μg GHRH, and after placebo. Compared with placebo, single GHRH significantly increased time spent in stage 4 sleep (p <.01) and in stage 2 sleep, reduced time spent in wakefulness and onset latency of stage 4 sleep (p < .05, for each), while repetitive GHRH remained without effects. GH secretory activity also tended to be higher after single than repetitive GHRH. Thus, results suggest the relevance of a transiently high concentration of GHRH in blood as an essential factor in enhancing the central nervous sleep process.