Endocrine Abstracts

Rhythmic, timed secretion of ghrelin and leptin is integral to the intricate temporal interplay of hormonal signals that maintains energy balance, feeding and body weight. Growth hormone replacement (GHR) in adult growth hormone deficient (AGHD) patients has been shown to alter body composition, energy balance and insulin sensitivity with changes in leptin secretory pattern and concentration. With GHR, single time point ghrelin concentrations have been shown to either increase, decrease or not change. Therefore, we studied the secretory pattern of ghrelin prior to and following GHR in AGHD and its relationship with leptin.

Methods: Blood samples were collected for ghrelin and leptin at half-hourly intervals over 24 h in 4 AGHD patients (2 men) prior to, then 1, 6 and 12 months following GHR. Circadian rhythm analysis (CHRONOLAB), pulse analysis (ULTRA) and cross correlation analyses were performed.

Results: Circulating ghrelin and leptin exhibited significant circadian rhythms (P<0.001) and ultradian pulsatility prior to and following GHR. Ghrelin concentrations were higher during the day (acrophase range – 16:30 to 17:40) and were out of phase with leptin which demonstrated higher nocturnal concentrations. Maximum negative cross-correlation coefficient was observed when changes in leptin concentration preceded changes in ghrelin by half an hour (r=−0.6). GHR had significant effects on the day-time and nocturnal concentration changes of both leptin and ghrelin as well as an increase in leptin pulsatility. Ghrelin secretion also showed an ultradian pulsatility with a mean of 7.3±1.3 pulses/24 h in untreated AGHD but with no significant change following GHR.

Discussion: GHR has significant effects on the secretory rhythm of both leptin and ghrelin which may contribute to the restoration of their organised, co-ordinated and timed secretion and inter-communication needed to favourably change and maintain energy balance, body composition and insulin sensitivity on a daily basis in treated AGHD patients.