Somatostatin infusion suppresses GH secretory burst frequency and mass in normal men

Calabresi, E.; Ishikawa, Eiji; Bartolini, L.; Delitala, G.; Fanciulli, Giuseppe; Oliva, Osvaldo; Veldhuis, Johannes D.; Serio, Mario

doi:10.1152/ajpendo.1996.270.6.e975

Cited by 24 publications

(17 citation statements)

References 24 publications

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“…IGF-I administration in this syndrome diminishes GH secretion, indicating that feedback can be restored (28). The amplified GH secretion is likely mediated by increased hypothalamic GHRH output, while somatostatin release is not affected in view of the unchanged GH pulsatility (29)(30)(31)(32).…”

Section: Discussionmentioning

confidence: 90%

Growth hormone secretion and immunological function of a male patient with a homozygous STAT5b mutation

et al. 2007

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Objective: STAT5b is a component of the GH signaling pathway. Recently, we described a 31-year-old male patient (height, K5.9 SDS) with a novel homozygous inactivating mutation in the STAT5b gene. The purpose of this study is to describe the phenotype in detail, including GH secretion and immunological function. In addition, we report four family members of this patient, all heterozygous carriers of the mutation. Design and methods: Twenty-four hour GH and prolactin secretion characteristics were assessed by blood sampling at 10-min intervals. An IGF-I generation test was performed. Monocyte function was tested by stimulation of whole blood with lipopolysaccharide (LPS) in the presence or absence of Interferon-g (IFN-g). In addition, T cell function was determined by measuring proliferative responses of peripheral blood mononuclear cells (PBMC) after stimulation by various polyclonal activators and Interleukin-2 (IL-2). Clinical and biochemical characteristics were determined in the carriers of the mutation. Results: GH secretory parameters were comparable with that of healthy male controls (mean fat percentage 25), but likely increased in relation to the patient's 40% body fat. The regularity of GH secretion was diminished. Prolactin secretion was increased by sixfold. The IGF-I generation test showed a small increase in IGF-I and IGF-binding protein-3 on lower GH doses and an increase in IGF-I to K2.4 SDS on the highest dose of GH. In vitro, IL-12p40, IL 10, and tumour necrosis factor-a (TNF-a) production rates by PBMC increased to values within the normal range upon stimulation of LPS. Heterozygous carriers of the mutation did not show abnormalities, although the height of the males was below the normal range. Conclusions: This report shows that GH and prolactin secretion were increased in this patient homozygous for a new STAT5b mutation. Although STAT5b plays a role in signaling within immune cells, clinical immunodeficiency is not an obligatory phenomenon of STAT5b deficiency per se. Heterozygous carriers of a STAT5b mutation show no signs of GH insensitivity. 156 155-165 European Journal of Endocrinology

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Section: Discussionmentioning

confidence: 90%

Growth hormone secretion and immunological function of a male patient with a homozygous STAT5b mutation

et al. 2007

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“…From a mechanistic vantage, the size of GH secretory bursts is determined by specific peptide signals that mediate feedforward [GH-releasing hormone (GHRH), GH-releasing peptide (GHRP)/ghrelin] and feedback [GH, insulin-like growth factor I (IGF-I), and somatostatin (SS)] (3,5,7,9,18,22,32,38,42,47). In this context, what remains difficult to parse includes 1) which particular secretagogues are affected by age, estrogen, and adiposity; 2) the relative contributions that age, sex steroids, and AVF make to the regulation of GH secretion; 3) the degree to which the same three covariates interact pairwise or altogether to determine GH production; and 4) the differential impact of age, sex hormones, and AVF on pulsatile vis-à-vis basal GH secretion.…”

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confidence: 99%

Relative effects of estrogen, age, and visceral fat on pulsatile growth hormone secretion in healthy women

Veldhuis

Hudson

Erickson

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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Relative effects of estrogen, age, and visceral fat on pulsatile growth hormone secretion in healthy women. Am J Physiol Endocrinol Metab 297: E367-E374, 2009. First published May 26, 2009 doi:10.1152/ajpendo.00230.2009.-Growth hormone (GH) secretion is subject to complex regulation. How pre-and postmenopausal age (PRE, POST), estradiol (E2) availability, and abdominal visceral fat (AVF) jointly affect peptidyl-secretagogue drive of GH secretion is not known. To this end, healthy PRE (n ϭ 20) and POST (n ϭ 22) women underwent a low-vs. high-E 2 clamp before receiving a continuous intravenous infusion of GH-releasing hormone (GHRH) or GH-releasing peptide (GHRP-2). According to analysis of covariance, PRE and POST women achieved age-independent hypo-and euestrogenemia under respective low-and high-E 2 clamps. All four of age (P Ͻ 0.001), E2 status (P ϭ 0.006), secretagogue type (P Ͻ 0.001), and an age ϫ peptide interaction (P ϭ 0.014) controlled pulsatile GH secretion. Independently of E 2 status, POST women had lower GH responses to both GHRH (P ϭ 0.028) and GHRP-2 (P Ͻ 0.001) than PRE women. Independently of age, GHRP-2 was more stimulatory than GHRH during low E 2 (P ϭ 0.011) and high E2 (P Ͻ 0.001). Stepwise forward-selection multivariate analysis revealed that computerized tomographic estimates of AVF explained 22% of the variability in GHRH action (P ϭ 0.002), whereas age and E 2 together explained 60% of the variability in GHRP-2 drive (P Ͻ 0.001). These data establish that age, estrogen status, and AVF are triple covariates of continuous peptide-secretagogue drive of pulsatile GH secretion in women. Each factor must be controlled for to allow valid comparisons of GH-axis activity.somatotropin; growth hormone-releasing hormone; growth hormone secretion; growth hormone-releasing peptide; human; estrogen GROWTH HORMONE (GH) secretion is predominantly (Ͼ85%) pulsatile in healthy young adults (20). The first day of infant life, Tanner stages IV-V of puberty, and the late-follicular phase of the menstrual cycle are associated with severalfold augmentation of the mass (size) of GH secretory bursts with no evident changes in GH secretory-burst frequency or GH halflife (54). Conversely, midchildhood, hypogonadism in young adults, older age, low aerobic capacity, and adiposity are accompanied by a marked diminution in pulsatile GH production (8,17,29,30,33,44,55).Although the factors that control basal (nonpulsatile) GH secretion are not well known, pulsatile GH secretion is stimulated by fasting, aromatizable androgens, and estradiol (E 2 ) but attenuated by factors associated with food intake, abdominal visceral fat (AVF), and aging (11,19,23,29,31,39,44, 45,48). From a mechanistic vantage, the size of GH secretory bursts is determined by specific peptide signals that mediate feedforward [GH-releasing hormone (GHRH), GH-releasing peptide (GHRP)/ghrelin] and feedback [GH, insulin-like growth factor I (IGF-I), and somatostatin (SS)] (3,5,7,9,18,22,32,38,42,47). In this context, what remains difficult to parse inc...

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“…Additional complexities are imposed by nutritional status, sex steroid milieu, and feedback by insulin-like growth factor (IGF) I and GH. In humans, where hypophysial-portal sampling is not feasible, the roles of GHRH and somatostatin have been inferred from studies with continuous, presumably saturating infusions of GHRH, GHS, and somatostatin or its analogs (7,13,32,35,61,72,79) as well as by the use of a GHRH antagonist (33,34). These studies have provided evidence for a predominant role of GHRH and an additive role of somatostatin in GH pattern regulation in humans.…”

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confidence: 99%

Pulsatile growth hormone secretion persists in genetic growth hormone-releasing hormone resistance

Maheshwari

Pezzoli

Rahim

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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. Pulsatile growth hormone secretion persists in genetic growth hormone-releasing hormone resistance. Am J Physiol Endocrinol Metab 282: E943-E951, 2002. First published January 8, 2002 10.1152/ajpendo.00537.2001 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 (Ͻ1% 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.growth hormone-releasing hormone receptor; somatostatin; pituitary gland; short stature GROWTH HORMONE (GH) IS SECRETED in a pulsatile or episodic manner. This secretion pattern is principally governed by hypothalamic growth hormone-releasing hormone (GHRH) and somatostatin (see Ref. 23 for review). Ghrelin (39) and/or a similar endogenous ligand for the GH secretagogue (GHS) receptor may also participate in GH pulse generation, although its role in physiological GH secretion is still largely unknown. GHRH and ghrelin stimulate pituitary GH release, whereas somatostatin inhibits it. In addition to its acute GH-releasing action, GHRH also stimulates GH synthesis (3) and somatotrope proliferation during pituitary ontogeny (41, 68).The pulsatile pattern of GH secretion and its relation to GHRH and somatostatin rhythms has been evaluated extensively in a number of species (23), and a concept of GHRH-induced GH pulses, modulated by prevailing somatostatin tone and rapid somatostatin oscillations, has been formulated (65). A role of ghrelin in this interplay can be postulated but remains unproved. This model is supported by studies using immunoneutralization of GHRH and somatostatin (65, 80), GHRH, or somatostatin antagonists (5,33,34,73), as well as direct pituitary portal sampling in experimental animals (18,20,55,66). A reciprocal relationship between GHRH and somatostatin, where GHRH pulses coincide with somatostatin troughs, has been reported in rats (37,55,65), but this pattern is less clear in sheep or pigs, where more complex relationships between oscillations in GHRH, somatostatin, and GH prevail (8,15,20,66). Thus important species as well as sex differences exist in the regulation...

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Somatostatin infusion suppresses GH secretory burst frequency and mass in normal men

Cited by 24 publications

References 24 publications

Growth hormone secretion and immunological function of a male patient with a homozygous STAT5b mutation

Growth hormone secretion and immunological function of a male patient with a homozygous STAT5b mutation

Relative effects of estrogen, age, and visceral fat on pulsatile growth hormone secretion in healthy women

Pulsatile growth hormone secretion persists in genetic growth hormone-releasing hormone resistance

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