Might also exert an inhibitory effect on ghrelin

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might also exert an inhibitory effect on ghrelin secretion (32–34). However, in our fasting individuals a spontaneous ghrelin decrease was observed which occurred later compared with non-fasting subjects and without a marked change in insulin or glucose levels. This indicates mechanisms at a neuronal level which are independent of gastric stimuli. We found a significant decrease in ghrelin levels over a 24-h period (Fig. 3) which was not observed in non– fasting subjects (11). In accordance with this, individ- ual hunger perception, as rated on a scale from 1 to 10 by the probands, decreased during the second half of the observation period (data not shown). The spontaneous secretion pattern of ghrelin as ana- lysed by the Cluster algorithm demonstrated a charac- teristic pulsatility with a frequency of 8.3 ^ 0.9 pulses over a 24-h period. This further indicates that neuronal rather than gastrointestinal signals might be operative in the modulation of ghrelin secretion. Accordingly, Table 1 Subjects’ characteristics and results from Cluster analysis of ghrelin levels during the 24-h fasting period. Subject Sex Age (years) BMI (kg/m 2 ) [SDS] No. of peaks Mean interval between peaks (min) Mean peak width (min) Mean pulse amplitude (pg/ml) 1 F 28.6 20.0 [ 2 0.67] 8 157.1 ^ 57.1 117.5 ^ 16.7 715.2 ^ 135.4 2 F 21.9 20.3 [ 2 0.56] 7 176.7 ^ 36.7 125.7 ^ 59.7 707.1 ^ 83.5 3 F 19.0 21.8 [0] 10 122.2 ^ 56.1 92.0 ^ 62.7 411.8 ^ 64.7 4 M 30.0 23.8 [0.62] 8 148.6 ^ 54.0 130.0 ^ 51.3 686.0 ^ 123.4 5 M 25.0 24.3 [0.81] 9 132.5 ^ 36.9 111.1 ^ 60.9 185.8 ^ 51.0 6 M 28.6 26.6 [1.68] 8 151.4 ^ 73.8 115.0 ^ 53.2 348.9 ^ 179.2 SDS, standard deviation score. 100 200 300 400 500 600 700 800 8:00 12:00 16:00 20:00 0:00 4:00 8:00 Ghrelin (pg/ml) Clock time (h) Figure 3 Average total plasma ghrelin profile from all 6 subjects (central thick line), and average plasma ghrelin profile from three high level and from three low level subjects (upper and lower lines respectively). Note the overall decrease in ghrelin levels during the 24-h fasting period. 0 100 200 300 400 500 600 700 800 900 1000 8:00 12:00 16:00 20:00 0:00 4:00 8:00 Clock time (h) Ghrelin (pg/ml) Figure 4 Characteristic 24-h fasting plasma ghrelin profiles from two subjects. ( ) represent pulses as identified by Cluster analysis. 848 G Natalucci and others EUROPEAN JOURNAL OF ENDOCRINOLOGY (2005) 152
rats showed a higher ghrelin pulse frequency during 3 h of fasting than in a fed state (35). We found considerable interindividual variation in plasma ghrelin levels among the six subjects (Fig. 1). Interestingly, higher profiles were found in the two females with the lower BMIs and in the male with the lowest BMI as compared with the other males. These data are in agreement with other observations in adults and children demonstrating the influence of body constitution and nutritional status on circulating ghrelin levels (9, 10, 26) and possibly support the obser- vation of sexual dimorphism of circulating ghrelin con- centrations, with higher levels found in females (32, 36). It is well known that ghrelin administration will stimulate GH secretion (2, 37). Furthermore, a syn- chronicity of ghrelin and GH was seen during various nutritional regimes (32). However, under fasting con- ditions we did not find any correlation between these two hormones. Both ghrelin and GH were secreted in

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