Dual Defects in Pulsatile Growth Hormone Secretion and Clearance Subserve the Hyposomatotropism of Obesity in Man*

Abstract

We have examined the mechanisms underlying reduced circulating GH concentrations in the obese human. Computer-assisted (deconvolution) analysis was used to determine endogenous GH secretory and clearance rates quantitatively from entire 24-h plasma GH concentration profiles. These analyses revealed that the half-life (t 1/2) of endogenous GH was significantly shorter in obese (11.7 +/- 1.6 min) than in normal weight subjects (15.5 +/- 0.81 min; P less than 0.01). The accelerated blood disposal rate of GH was not due to decreased circulating concentrations of GH-binding protein, since the latter were similar in obese (25 +/- 1.0%) and normal weight (24 +/- 2.3%) men. However, obese men had significantly fewer GH secretory bursts (3.2 +/- 0.53 vs. 9.7 +/- 0.67/day; P less than 0.01). Among the rare GH secretory bursts that occurred in obese subjects, there were significantly prolonged mean intersecretory burst intervals (282 +/- 65 vs. 131 +/- 11 min; P less than 0.05). The resultant daily GH production rate in obese men was reduced to one fourth that in normal weight individuals. Both GH secretion rate and burst frequency were negatively correlated with the degree of obesity (ponderal index). The decreases in GH burst frequency and half-life were specific, since GH secretory pulse amplitude (maximal rate of GH release), the mass of GH released per burst, and the duration of computer-resolved GH secretory bursts were not different in obese and normal weight men. We conclude that obese men harbor a double defect in GH dynamics involving both GH secretion and clearance, and that the severity of the GH secretory deficiency is proportionate to the degree of obesity.

Obesity and the polycystic ovary syndrome

“…32 In addition, in obese subjects an increased GH metabolic clearance rate has been described. 33 Although mechanisms have not been fully elucidated, there is evidence that elevated FFA levels and increased insulin levels may play a pivotal role in determining reduced GH levels in obesity. Therefore, it is realistic to speculate that similar mechanisms may play a role in obese PCOS women.…”

Role of obesity and leptin in the pubertal process and pubertal growth—a review

“…[61][62][63] Measurements performed during sleep and over 24 h have shown that GH secretion in obese children is reduced not only under physiological conditions, but also following pharmacologic stimulation with insulin, clonidine, arginine, levodopa, glucagon, GH-releasing hormone, and opiate peptides, much like in children with GH deficiency. 64 Despite the reduction in circulating GH levels, obese children may have normal, increased or reduced, plasma IGF-I and GH-binding protein levels.…”

Aspectos neuroendócrinos da síndrome metabólica

“…Diversos estudos já comprovaram que o aumento do IMC está relacionado a uma diminuição na meia-vida (46), na produção, na freqüên-cia e na amplitude (47) dos episódios secretórios do GH. De uma forma geral, a taxa de secreção e produção do GH diminui em 6% para cada unidade aumentada no IMC e é quase 4 vezes menor em pacientes obesos do que em controle normais (46). A diminuição na liberação do GH também já foi evidenciada em crianças (48) e adolescentes obesos (49) e correlaciona-se indireta-…”