Dual defects in pulsatile growth hormone secretion and clearance subserve the hyposomatotropism of obesity in man

Johannes D Veldhuis, Ali Iranmanesh, Ken K Y Ho, Michael J. Waters, Michael L. Johnson, German Lizarralde

Research output: Contribution to journalArticle

421 Scopus citations

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 (t1/2) of endogenous GH was significantly shorter in obese (11.7 ± 1.6 min) than in normal weight subjects (15.5 ± 0.81 min; P < 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 < 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 < 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.

Original languageEnglish (US)
Pages (from-to)51-59
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume72
Issue number1
StatePublished - Jan 1991
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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    Veldhuis, J. D., Iranmanesh, A., Ho, K. K. Y., Waters, M. J., Johnson, M. L., & Lizarralde, G. (1991). Dual defects in pulsatile growth hormone secretion and clearance subserve the hyposomatotropism of obesity in man. Journal of Clinical Endocrinology and Metabolism, 72(1), 51-59.