Enhanced Response of Human Circulating Erythroid Progenitor Cells to hGH and to IGF-I in Children with Insufficient Growth Hormone Secretion

Abstract The physiological role of endogenous circulating GHreleasing hormone (GHRH) and somatostatin (SRIH) on spontaneous pulsatile and neostigmine-induced secretion of GH was investigated in adult rams actively immunized against each neuropeptide. All animals developed antibodies at concentrations sufficient for immunoneutralization of GHRH and SRIH levels in hypophysial portal blood. In the anti GHRH group, plasma GH levels were very low; the amplitude of GH pulses was strikingly reduced, although their number was unchanged. No stimulation of GH release was observed after neostigmine administration. The reduction of GH secretion was associated with a decreased body weight and a significant reduction in plasma IGF-I concentration. In the antiSRIH group, no changes in basal and pulsatile GH secretion or the GH response to neostigmine were observed as compared to controls. Body weight was not significantly altered and plasma IGF-I levels were reduced in these animals. These results suggest that in sheep, circulating SRIH (in the systemic and hypophysial portal vasculature) does not play a significant role in pulsatile and neostigmine-induced secretion of GH. The mechanisms of its influence on body weight and production of IGF-I remain to be determined. Journal of Endocrinology (1995) 144, 83–90

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Negative feedback of insulin-like growth factor-I on growth hormone secretion by porcine pituitary cells

Canadian Journal of Animal Science ◽

10.4141/cjas95-007 ◽

1995 ◽

Vol 75 (1) ◽

pp. 57-61 ◽

Cited By ~ 1

Author(s):

C. Farmer ◽

H. Lapierre

Keyword(s):

Growth Hormone ◽

Negative Feedback ◽

Culture Media ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Late Gestation ◽

Pituitary Cells ◽

Gh Secretion ◽

Age Related ◽

Igf I

Pituitaries from female Yorkshire pig fetuses (90 d, n = 26; 110 d, n = 17) and 6-mo-old pigs (n = 5) were enzymatically dispersed, plated, and cultured for 47 h. The cells were then rinsed and incubated for 22 h with testing media containing 0, 50, 100, 200, 300 or 400 ng mL−1 of IGF-I. Half of the wells from each concentration of IGF-I were then incubated for an additional 3 h with concentrations of IGF-I similar to those in the previous incubation, while the other half also had GRF added to the testing media to reach a final concentration of 10−8 M. Culture media were then collected from all the wells, were frozen, and later assayed for GH. Irrespective of whether GRF was present, IGF-I decreased pituitary secretion of GH (P < 0.001). A significant negative response to IGF-I was already present at the dose of 50 ng mL−1 (P < 0.0001). However, the extent of the GH response to IGF-I seen in pigs of various ages differed depending on whether GRF was present. The present results therefore establish that IGF-I does exert a negative feedback on pituitary GH secretion in swine and that the age-related changes in this feedback are dependent on the presence of GRF. In swine, it appears that high circulating concentrations of GH in late-gestation fetuses are not a result of a lesser sensitivity of the somatotroph to the inhibitory actions of IGF-I. Key words: Pig, cell culture, pituitary, IGF-I, growth hormone, age

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Regulated recovery of pulsatile growth hormone secretion from negative feedback: a preclinical investigation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00293.2011 ◽

2011 ◽

Vol 301 (4) ◽

pp. R1143-R1152 ◽

Cited By ~ 3

Author(s):

Johannes D. Veldhuis ◽

Cyril Y. Bowers

Keyword(s):

Body Mass Index ◽

Growth Hormone ◽

Body Mass ◽

Negative Feedback ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Gh Secretion ◽

Model Free ◽

Preclinical Investigation ◽

Igf I

Although stimulatory (feedforward) and inhibitory (feedback) dynamics jointly control neurohormone secretion, the factors that supervise feedback restraint are poorly understood. To parse the regulation of growth hormone (GH) escape from negative feedback, 25 healthy men and women were studied eight times each during an experimental GH feedback clamp. The clamp comprised combined bolus infusion of GH or saline and continuous stimulation by saline GH-releasing hormone (GHRH), GHRP-2, or both peptides after randomly ordered supplementation with placebo (both sexes) vs. E2 (estrogen; women) and T (testosterone; men). Endpoints were GH pulsatility and entropy (a model-free measure of feedback quenching). Gender determined recovery of pulsatile GH secretion from negative feedback in all four secretagog regimens (0.003 ≤ P ≤ 0.017 for women>men). Peptidyl secretagog controlled the mass, number, and duration of feedback-inhibited GH secretory bursts (each, P < 0.001). E2/T administration potentiated both pulsatile ( P = 0.006) and entropic ( P < 0.001) modes of GH recovery. IGF-I positively predicted the escape of GH secretory burst number and mode ( P = 0.022), whereas body mass index negatively forecast GH secretory burst number and mass ( P = 0.005). The composite of gender, body mass index, E2, IGF-I, and peptidyl secretagog strongly regulates the escape of pulsatile and entropic GH secretion from autonegative feedback. The ensemble factors identified in this preclinical investigation enlarge the dynamic model of GH control in humans.

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What should be the diagnosis and management of short children with normal growth hormone secretion and non-primary IGF-I deficiency?

Pediatric Endocrinology ◽

10.18544/ep-01.13.04.1498 ◽

2014 ◽

Vol 13 (4) ◽

pp. 9-18

Author(s):

Joanna Smyczyńska ◽

◽

Renata Stawerska ◽

Andrzej Lewiński ◽

◽

...

Keyword(s):

Growth Hormone ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Normal Growth ◽

Diagnosis And Management ◽

Short Children ◽

Igf I

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Growth hormone secretion in response to glucagon stimulation test in healthy middle-aged men

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302009000700009 ◽

2009 ◽

Vol 53 (7) ◽

pp. 853-858 ◽

Cited By ~ 15

Author(s):

Eduardo Micmacher ◽

Roberto P. Assumpção ◽

Renato G. Redorat ◽

Luciana D. Spina ◽

Ivan C. Cruz ◽

...

Keyword(s):

Growth Hormone ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Tolerance Test ◽

Stimulation Test ◽

Hormone Deficiency ◽

Glucagon Stimulation Test ◽

Healthy Men ◽

Positive Correlation ◽

Igf I

OBJECTIVE: To investigate the growth hormone (GH) response to glucagon stimulation test (GST) in a population of healthy men over 50 years old in comparison to insulin tolerance test (ITT), analysis of the spontaneous 24-hour GH profile and insulin-like growth factor 1 (IGF-I). METHODS: 27 healthy men aged between 51 and 65 years were tested. RESULTS: Using non-parametric correlation analysis, a positive correlation between GH peak after GST and mean IGF-I (r = 0.528; p = 0.005) was found, as well with GH peak in 24-hour profile (r = 0.494; p = 0.009). No correlation was found comparing GH peak after ITT with the same parameters. Ten subjects presented GH peak of less than 3.0 μg/L after GST, none confirmed in ITT. CONCLUSIONS: GH peak response to GST was lower than ITT, but it showed a positive correlation with mean IGF-I and also with GH peak in 24-hour profile. However, GST should not be used to differentiate organic growth hormone deficiency (GDH) from the expected decline on GH secretion due to aging.

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Effect of Zinc Supplementation on Growth Hormone Secretion, IGF-I, IGFBP-3, Somatomedin Generation, Alkaline Phosphatase, Osteocalcin and Growth in Prepubertal Children with Idiopathic Short Stature

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem.2005.18.1.69 ◽

2005 ◽

Vol 18 (1) ◽

Cited By ~ 25

Author(s):

Sebahat Imamoglu ◽

Abdullah Bereket ◽

Serap Turan ◽

Yavuz Taga ◽

Goncagül Haklar

Keyword(s):

Growth Hormone ◽

Alkaline Phosphatase ◽

Short Stature ◽

Zinc Supplementation ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Idiopathic Short Stature ◽

Prepubertal Children ◽

Igf I ◽

Igfbp 3

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Cycloheximide blocks insulin-like growth factor I but not somatostatin inhibition of growth hormone secretion

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y87-088 ◽

1987 ◽

Vol 65 (4) ◽

pp. 515-519 ◽

Cited By ~ 5

Author(s):

M. S. Sheppard ◽

R. M. Bala

Keyword(s):

Growth Hormone ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Protein Synthesis Inhibitor ◽

Hormone Release ◽

Growth Hormone Release ◽

Synthesis Inhibitor ◽

Inhibition Of Growth ◽

Igf I

Growth hormone secretion is controlled by the two hypothalamic hormones, growth hormone releasing factor (GRF) and somatostatin. In addition, the insulin-like growth factors (IGF or somatomedins) which are themselves growth hormone dependent, inhibit growth hormone release in vitro, therefore acting to close the negative feedback loop. The studies reported here examine some of the differences between inhibition of growth hormone secretion by somatostatin and IGF-I in vitro. The major finding is that cycloheximide, a protein synthesis inhibitor, blocks inhibition of GRF-stimulated growth hormone release caused by IGF-I, without changing the inhibition caused by somatostatin. The experiments were done by exposing mixed rat adenohypophysial cells to secretagogues with or without cycloheximide for 24 h in a short term culture. Somatostatin (0.6 nM) totally blocked rat GRF (1 nM) stimulated growth hormone release to values 48% of control (nonstimulated values), while IGF-1 (27 nM) only reduced the GRF-stimulated growth hormone release by 27 ± 3% (N = 5). Cycloheximide (15 μg/mL) totally blocked the effect of IGF-I but not somatostatin. A low concentration (0.12 nM) of somatostatin, which only partly inhibited growth hormone release, was also unaffected by cycloheximide. In purified rat somatotrophs, somatostatin (0.1 nM) inhibited GRF-stimulated cAMP levels slightly and reduced growth hormone release while IGF-I (40 nM) had no effect. We suggest that IGF-I inhibits only the secretion of newly synthesized growth hormone, while somatostatin inhibits both stored and newly synthesized growth hormone pools.

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Ontogeny of growth hormone, insulin-like growth factor-I, estradiol and cortisol in the growing lamb: effect of testosterone

Journal of Endocrinology ◽

10.1677/joe.0.1500391 ◽

1996 ◽

Vol 150 (3) ◽

pp. 391-399 ◽

Cited By ~ 18

Author(s):

A M Arnold ◽

J M Peralta ◽

M L Thonney

Keyword(s):

Growth Hormone ◽

Growth Factor ◽

Hormone Secretion ◽

Muscle Growth ◽

Growth Hormone Secretion ◽

Testosterone Replacement Therapy ◽

Insulin Like Growth Factor ◽

Factor I ◽

Igf I ◽

Growth Factor I

Abstract Exogenous sex steroids have altered growth hormone secretion in some domestic species. This study examined whether different physiological concentrations of testosterone alter muscle growth in sheep through modification of the somatotropic axis. The effects of testosterone on growth hormone (GH), insulin-like growth factor-I (IGF-I), estradiol (E2) and cortisol concentrations in growing lambs were evaluated in 20 rams, 20 wethers and 20 wethers receiving subcutaneous testosterone replacement therapy. Two animals from each of the three testosterone status groups were slaughtered at 14-day intervals from 49 to 133 days of age, and then at 28-day intervals until 217 days of age for a total of 10 slaughter ages. Animals were sampled every 10 min for an 8-h period 1 day prior to slaughter to characterize the episodic patterns of GH and testosterone. Immediately after slaughter, the semitendinosus, splenius and triceps brachii muscles were removed, trimmed of adhering fat and connective tissue, and weighed. Testosterone increased the combined muscle weight. GH concentrations decreased during the course of the experiment. However, there was no effect of testosterone on GH mean, baseline, amplitude or GH pulse frequency measured by PULSAR. IGF-I concentrations increased in response to testosterone treatment. Testosterone had no effect on cortisol levels while E2 levels were increased after 133 days. Increased muscle growth due to testosterone appeared to be caused either by a direct effect or by increased levels of IGF-I independent of circulating GH concentrations. Journal of Endocrinology (1996) 150, 391–399

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