The acute leptin response to GH.
The effect of an acute bolus of GH on serum leptin in normal individuals and the factors affecting this response have not previously been studied. Seventeen healthy volunteers with normal body mass index, with ages ranging from 20.5-78.2 yr were studied. Each subject received three single doses of GH in random order at least 4 wk apart. Bioimpedence analysis was performed to provide estimates of fat and lean masses. Serum samples for leptin, insulin, and IGF-I were taken 0, 18, 24, 48, 72, and 120 h after each dose of GH. Leptin levels changed significantly after the 0.67- and 7-mg doses of GH, but not after the 0.27-mg dose. Compared with baseline, there was a significant elevation (P < 0.001) in serum leptin levels at 24 h, followed by a significant decrease (P < 0.01) at 72 h. Baseline and peak leptin levels were significantly determined by gender, fat mass, and log(10) insulin. Nadir leptin levels were significantly determined by gender and fat mass. In contrast, the increment in leptin levels was significantly determined by age, although this only accounted for 24% of the variability in the increment in leptin levels. We have demonstrated that administration of a single bolus dose of GH significantly increases serum leptin levels, followed by a significant nadir. This occurs not only after a supraphysiological dose of GH, but also after 0.67 mg, a dose within the physiological replacement range. The increment in leptin increases with advancing age, suggesting that at the level of the adipocyte, aging increases responsiveness to GH. However, this only partially explains the changes seen, and it is likely that another factor(s) is involved in the acute impact of GH on circulating leptin levels. The presence of a significant nadir after the peak in leptin levels supports the existence of a negative feedback loop, linking circulating leptin to its own biosynthesis in adipose tissue, mediated by peripheral leptin receptors. These data provide unequivocal evidence that GH can affect serum leptin levels in the absence of a change in body composition.
Lissett
C A
CA
Department of Endocrinology, Christie Hospital, Manchester, United Kingdom M20 4BX.
Clayton
P E
PE
Shalet
S M
SM
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D005260:Female; D013006:Growth Hormone / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics
D007328:Insulin; D020738:Leptin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone