In a study where GH secretion was stimulated by the injection of growth hormone releasing hormone (GHRH) at the beginning of the sleep period, it was found that whenever sleep was interrupted by a spontaneous awakening, the ongoing GH secretion was abruptly suppressed (41). This inhibitory effect of awakenings on the GH response to GHRH was further demonstrated in a detailed study where sleeping subjects who had received a GHRH injection were awakened 30 min after the injection and then allowed to re-initiate sleep 30 min later (42). The subjects who were able to resume sleep rapidly showed a secondary smaller GH pulse. A near complete inhibition of the GH response to GHRH was also observed when the injection was given 20 min after a forced awakening around the end of the first third of nocturnal sleep (42). It has been suggested that this inhibitory effect of nocturnal awakenings on the GH secretory response to GHRH could be mediated by an increase in somatostatin release (42). This increase in somatostatinergic activity could be effected by an increase in corticotropic activity. Indeed, awakenings during sleep are consistently associated with a pulse of cortisol secretion (43), and corticotropin-releasing hormone (CRH) administration may inhibit the GH response to GHRH stimulation (44).
These findings suggest that sleep fragmentation (a hallmark of aging ) will generally decrease nocturnal GH secretion and are particularly interesting in view of the well documented age-related decreases in GH secretion that occur in both men and women (13,46). Furthermore, the important effects of sleep and awakening on the secretory response to GHRH injection indicate that the state of wakefulness of the subject should be carefully monitored during testing with GHRH to prevent naps which could markedly influence the response.
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