title: Pulsatile growth hormone secretion persists in genetic growth hormone-releasing hormone resistance.
abstract: Growth hormone (GH) secretion is regulated by GH-releasing hormone (GHRH), somatostatin, and possibly ghrelin, but uncertainty remains about the relative contributions of these hypophysiotropic factors to GH pulsatility. Patients with genetic GHRH receptor (GHRH-R) deficiency present an opportunity to examine GH secretory dynamics in the selective absence of GHRH input. We studied circadian GH profiles in four young men homozygous for a null mutation in the GHRH-R gene by use of an ultrasensitive GH assay. Residual GH secretion was pulsatile, with normal pulse frequency, but severely reduced amplitude (<1% normal) and greater than normal process disorder (as assessed by approximate entropy). Nocturnal GH secretion, both basal and pulsatile, was enhanced compared with daytime. We conclude that rhythmic GH secretion persists in an amplitude-miniaturized version in the absence of a GHRH-R signal. The nocturnal enhancement of GH secretion is likely mediated by decreased somatostatin tone. Pulsatility of residual GH secretion may be caused by oscillations in somatostatin and/or ghrelin; it may also reflect intrinsic oscillations in somatotropes.
authors.affiliation: Center for Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Northwestern University Medical School, and Veterans Administration Chicago Health System, Lakeside Division, Chicago, Illinois 60611, USA.
authors.forename: Hiralal G
authors.initials: HG
authors.lastname: Maheshwari
authors.forename: Suzan S
authors.initials: SS
authors.lastname: Pezzoli
authors.forename: Asad
authors.initials: A
authors.lastname: Rahim
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Shalet
authors.forename: Michael O
authors.initials: MO
authors.lastname: Thorner
authors.forename: Gerhard
authors.initials: G
authors.lastname: Baumann
mesh_terms: D000328:Adult; D002940:Circadian Rhythm; D004351:Drug Resistance / Q000235:genetics; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006720:Homozygote; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009842:Oligopeptides / Q000494:pharmacology; D018013:Receptors, Neuropeptide / Q000172:deficiency / Q000235:genetics*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000172:deficiency / Q000235:genetics*; D013816:Thermodynamics
chemical_list: D009842:Oligopeptides; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; C086184:hexarelin; D019382:Human Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C048250:somatotropin releasing hormone receptor