Growth hormone (GH) secretion in patients with an inactivating defect of the GH-releasing hormone (GHRH) receptor is pulsatile: Evidence for a role for non-GHRH inputs into the generation of GH pulses

Ferdinand Roelfsema, Nienke R. Biermasz, Ronald Groote Veldman, Johannes D Veldhuis, Marijke Frölich, W. Henriëtte Stokvis-Brantsma, Jan Maarten Wit

Research output: Contribution to journalArticle

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Abstract

GH secretion is regulated by the interaction of GHRH and somatostatin and is released in 10-20 pulses in each 24-h cycle. The exact roles in pulse generation played by somatostatin, GHRH, and the recently isolated GH-releasing peptide, Ghrelin, are not fully elucidated. To investigate the GHRH-mediated GH secretion in human, we investigated pulsatile, entropic, and 24-h rhythmic GH secretion in two young adults (male, 24 yr; female, 23 yr) from a Moroccan family with a novel inactivating defect of the GHRH receptor gene. Data were compared with values in age- and gender-matched controls. Plasma GH concentration were measured by a sensitive immunofluorometric assay, with a detection limit of 0.01 mU/L. All plasma GH concentrations in the female patient were measurable; in the male patient 30 of 145 samples were at or below the detection limit. GH secretion was pulsatile, with 21 and 23 secretory episodes/24 h in the male and female patients, respectively. The fraction of basal to total GH secretion was raised in both patients by 0.18 and 0.15, respectively. The total 24-h GH production rate was greatly diminished; in the male patient it was 6.9 mU/L (normal values for his age, 26-63 mU/L), and in the female patient it was 4.2 mU/L (normal values for her age, 96-390 mU/L). The nyctohemeral plasma GH rhythm was preserved (P < 0.001), with normal acrophases (0430 and 0218 h in the male and female, respectively). Approximate entropy was greatly elevated in both subjects (0.82 in the male and 1.17 in the female; upper normal values for age and gender, 0.24 and 0.59, respectively). Intravenous injection of 50 μg GHRH failed to increase the plasma GH concentration in both patients, but 100 μg GH-releasing peptide-2 elicited a definite increase (male patient, 0.13 to 1.74 mU/L; female patient, 0.29 to 0.87 mU/L). Both patients had a partial empty sella on magnetic resonance imaging scanning. In summary, the present studies in two patients with a profound loss of function mutation of the GHRH receptor favor the view that in the human the timing of GH pulses is primarily supervised by intermittent somatostatin withdrawal, and the amplitude of GH pulses is driven by GHRH. In addition, we infer that effectual GHRH input controls the GH cell mass and the orderliness of the secretory process.

Original languageEnglish (US)
Pages (from-to)2459-2464
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume86
Issue number6
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Growth Hormone
Hormones
Defects
Somatostatin
Reference Values
Plasmas
Limit of Detection
somatotropin releasing hormone receptor
Fluoroimmunoassay
Growth Hormone-Releasing Hormone
Ghrelin
Human Growth Hormone
Secretory Pathway
Entropy
Intravenous Injections
Magnetic resonance
Young Adult
Magnetic Resonance Imaging
Assays
Genes

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Growth hormone (GH) secretion in patients with an inactivating defect of the GH-releasing hormone (GHRH) receptor is pulsatile : Evidence for a role for non-GHRH inputs into the generation of GH pulses. / Roelfsema, Ferdinand; Biermasz, Nienke R.; Veldman, Ronald Groote; Veldhuis, Johannes D; Frölich, Marijke; Henriëtte Stokvis-Brantsma, W.; Wit, Jan Maarten.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 86, No. 6, 2001, p. 2459-2464.

Research output: Contribution to journalArticle

Roelfsema, Ferdinand ; Biermasz, Nienke R. ; Veldman, Ronald Groote ; Veldhuis, Johannes D ; Frölich, Marijke ; Henriëtte Stokvis-Brantsma, W. ; Wit, Jan Maarten. / Growth hormone (GH) secretion in patients with an inactivating defect of the GH-releasing hormone (GHRH) receptor is pulsatile : Evidence for a role for non-GHRH inputs into the generation of GH pulses. In: Journal of Clinical Endocrinology and Metabolism. 2001 ; Vol. 86, No. 6. pp. 2459-2464.
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abstract = "GH secretion is regulated by the interaction of GHRH and somatostatin and is released in 10-20 pulses in each 24-h cycle. The exact roles in pulse generation played by somatostatin, GHRH, and the recently isolated GH-releasing peptide, Ghrelin, are not fully elucidated. To investigate the GHRH-mediated GH secretion in human, we investigated pulsatile, entropic, and 24-h rhythmic GH secretion in two young adults (male, 24 yr; female, 23 yr) from a Moroccan family with a novel inactivating defect of the GHRH receptor gene. Data were compared with values in age- and gender-matched controls. Plasma GH concentration were measured by a sensitive immunofluorometric assay, with a detection limit of 0.01 mU/L. All plasma GH concentrations in the female patient were measurable; in the male patient 30 of 145 samples were at or below the detection limit. GH secretion was pulsatile, with 21 and 23 secretory episodes/24 h in the male and female patients, respectively. The fraction of basal to total GH secretion was raised in both patients by 0.18 and 0.15, respectively. The total 24-h GH production rate was greatly diminished; in the male patient it was 6.9 mU/L (normal values for his age, 26-63 mU/L), and in the female patient it was 4.2 mU/L (normal values for her age, 96-390 mU/L). The nyctohemeral plasma GH rhythm was preserved (P < 0.001), with normal acrophases (0430 and 0218 h in the male and female, respectively). Approximate entropy was greatly elevated in both subjects (0.82 in the male and 1.17 in the female; upper normal values for age and gender, 0.24 and 0.59, respectively). Intravenous injection of 50 μg GHRH failed to increase the plasma GH concentration in both patients, but 100 μg GH-releasing peptide-2 elicited a definite increase (male patient, 0.13 to 1.74 mU/L; female patient, 0.29 to 0.87 mU/L). Both patients had a partial empty sella on magnetic resonance imaging scanning. In summary, the present studies in two patients with a profound loss of function mutation of the GHRH receptor favor the view that in the human the timing of GH pulses is primarily supervised by intermittent somatostatin withdrawal, and the amplitude of GH pulses is driven by GHRH. In addition, we infer that effectual GHRH input controls the GH cell mass and the orderliness of the secretory process.",
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T1 - Growth hormone (GH) secretion in patients with an inactivating defect of the GH-releasing hormone (GHRH) receptor is pulsatile

T2 - Evidence for a role for non-GHRH inputs into the generation of GH pulses

AU - Roelfsema, Ferdinand

AU - Biermasz, Nienke R.

AU - Veldman, Ronald Groote

AU - Veldhuis, Johannes D

AU - Frölich, Marijke

AU - Henriëtte Stokvis-Brantsma, W.

AU - Wit, Jan Maarten

PY - 2001

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N2 - GH secretion is regulated by the interaction of GHRH and somatostatin and is released in 10-20 pulses in each 24-h cycle. The exact roles in pulse generation played by somatostatin, GHRH, and the recently isolated GH-releasing peptide, Ghrelin, are not fully elucidated. To investigate the GHRH-mediated GH secretion in human, we investigated pulsatile, entropic, and 24-h rhythmic GH secretion in two young adults (male, 24 yr; female, 23 yr) from a Moroccan family with a novel inactivating defect of the GHRH receptor gene. Data were compared with values in age- and gender-matched controls. Plasma GH concentration were measured by a sensitive immunofluorometric assay, with a detection limit of 0.01 mU/L. All plasma GH concentrations in the female patient were measurable; in the male patient 30 of 145 samples were at or below the detection limit. GH secretion was pulsatile, with 21 and 23 secretory episodes/24 h in the male and female patients, respectively. The fraction of basal to total GH secretion was raised in both patients by 0.18 and 0.15, respectively. The total 24-h GH production rate was greatly diminished; in the male patient it was 6.9 mU/L (normal values for his age, 26-63 mU/L), and in the female patient it was 4.2 mU/L (normal values for her age, 96-390 mU/L). The nyctohemeral plasma GH rhythm was preserved (P < 0.001), with normal acrophases (0430 and 0218 h in the male and female, respectively). Approximate entropy was greatly elevated in both subjects (0.82 in the male and 1.17 in the female; upper normal values for age and gender, 0.24 and 0.59, respectively). Intravenous injection of 50 μg GHRH failed to increase the plasma GH concentration in both patients, but 100 μg GH-releasing peptide-2 elicited a definite increase (male patient, 0.13 to 1.74 mU/L; female patient, 0.29 to 0.87 mU/L). Both patients had a partial empty sella on magnetic resonance imaging scanning. In summary, the present studies in two patients with a profound loss of function mutation of the GHRH receptor favor the view that in the human the timing of GH pulses is primarily supervised by intermittent somatostatin withdrawal, and the amplitude of GH pulses is driven by GHRH. In addition, we infer that effectual GHRH input controls the GH cell mass and the orderliness of the secretory process.

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