Model informed quantification of the feed-forward stimulation of growth hormone by growth hormone releasing hormone

van Esdonk, M. J., Burggraaf, J., van der Graaf, P. H. & Stevens, J., 22-Feb-2020, In : British Journal of Clinical Pharmacology. 10 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Michiel J van Esdonk
  • Jacobus Burggraaf
  • Piet H van der Graaf
  • Jasper Stevens

AIMS: Growth hormone (GH) secretion is pulsatile and secretion varies highly between individuals. To understand and ultimately predict GH secretion, it is important to first delineate and quantify the interaction and variability in the biological processes underlying stimulated GH secretion. This study reports on the development of a population non-linear mixed effects model for GH stimulation, incorporating individual GH kinetics and the stimulation of GH by GH releasing hormone (GHRH).

METHODS: Literature data on the systemic circulation, the median eminence, and the anterior pituitary were included as system parameters in the model. Population parameters were estimated on data from 8 healthy normal weight and 16 obese women who received a 33 μg recombinant human GH dose. The next day, a bolus injection of 100 μg GHRH was given to stimulate GH secretion.

RESULTS: The GH kinetics were best described with the addition of 2 distribution compartments with a bodyweight dependent clearance (increasing linearly from 24.7 L/h for a 60 kg subject to 32.1 L/h for a 100 kg subject). The model described the data adequately with high parameter precision and significant inter-individual variability on the GH clearance and distribution volume. Additionally, high variability in the amount of secreted GH, driven by GHRH receptor activation, was identified (coefficient of variation = 90%).

CONCLUSIONS: The stimulation of GH by GHRH was quantified and significant inter-individual variability was identified on multiple parameters. This model sets the stage for further development of by inclusion of additional physiological components to quantify GH secretion in humans.

Original languageEnglish
Number of pages10
JournalBritish Journal of Clinical Pharmacology
Publication statusE-pub ahead of print - 22-Feb-2020

ID: 119127224