Serum α-klotho levels are not informative for the evaluation of growth hormone secretion in short children

2017 ◽  
Vol 30 (10) ◽  
Author(s):  
Cristina Meazza ◽  
Heba H. Elsedfy ◽  
Randa I. Khalaf ◽  
Fiorenzo Lupi ◽  
Sara Pagani ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Transmembrane Protein ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Serum Levels ◽  
Tolerance Test ◽  
Gh Secretion ◽  
Short Children ◽  
Egyptian Children ◽  
Igf I

AbstractBackground:α-Klotho is a transmembrane protein that can be cleaved and act as a circulating hormone (s-klotho). s-Klotho serum levels seem to reflect growth hormone (GH) secretory status. We investigated the role of s-klotho as a reliable marker of GH secretion in short children and the factors influencing its secretion.Methods:We enrolled 40 short Egyptian children (20 GH deficiency [GHD] and 20 idiopathic short stature [ISS]). They underwent a pegvisomant-primed insulin tolerance test (ITT) and were accordingly reclassified as 16 GHD and 24 ISS. The samples obtained before and 3 days after pegvisomant administration, prior to the ITT, were used for assaying insulin-like growth factor (IGF)-I and s-klotho.Results:IGF-I and s-klotho serum levels were not significantly different (p=0.059 and p=0.212, respectively) between GHD and ISS. After pegvisomant, a significant reduction in IGF-I and s-klotho levels was found in both groups. s-Klotho significantly correlated only with IGF-I levels in both groups.Conclusions:s-Klotho mainly reflects the IGF-I status and cannot be considered a reliable biomarker for GH secretion in children.

Effect of actively immunizing sheep against growth hormone-releasing hormone or somatostatin on spontaneous pulsatile and neostigmine-induced growth hormone secretion

1995 ◽  
Vol 144 (1) ◽  
pp. 83-90 ◽  
Author(s):  
E Magnan ◽  
L Mazzocchi ◽  
M Cataldi ◽  
V Guillaume ◽  
A Dutour ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Physiological Role ◽  
Gh Secretion ◽  
Igf I ◽  
Plasma Gh ◽  
Hypophysial Portal

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

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

1995 ◽  
Vol 75 (1) ◽  
pp. 57-61 ◽  
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

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

2011 ◽  
Vol 301 (4) ◽  
pp. R1143-R1152 ◽  
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.

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

2009 ◽  
Vol 53 (7) ◽  
pp. 853-858 ◽  
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.

Regulation by catecholamines of spontaneous growth hormone secretion in the baboon

1981 ◽  
Vol 241 (3) ◽  
pp. E196-E199
Author(s):  
J. K. Stewart ◽  
D. J. Koerker ◽  
C. J. Goodner ◽  
C. C. Gale ◽  
M. F. Minton ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Serum Levels ◽  
Adolescent Male ◽  
Serum Prolactin ◽  
Base Line ◽  
Spontaneous Growth ◽  
Fourfold Increase ◽  
Gh Secretion

To gain an increased understanding of the role of central neurotransmitters in the regulation of spontaneous growth hormone (GH) secretion in the primate, we investigated the effects of peripheral intravenous infusion of the alpha-adrenergic receptor-blocking agent, phentolamine (5.0-mg bolus and 1.5 mg . kg-1 . 12 h-1), and the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine (MPT, 300 mg . kg-1 . 24 h-1), on the pattern of GH secretion in five adolescent male baboons. Serum GH concentrations were measured in blood samples taken at 20-min intervals over 12 h (0530–1730) after an overnight fast. In nontreatment control studies, GH secretion exhibited a predictable rhythmic oscillation with a mean period of 5.7 +/- 0.4 (SE) h. Phentolamine significantly decreased the 12-h mean and integrated GH concentrations compared to control values, but the small peaks of GH, which could be distinguished from base-line concentrations in three of the animals, occurred at the same time as during control studies. Whereas alpha-methyl-p-tyrosine slightly reduced serum levels of GH, it significantly increased the GH pulse frequency in the baboons. A two- to fourfold increase in serum prolactin levels occurred in all animals treated with MPT. These findings suggest that alpha-adrenergic pathways play a stimulatory role in maintaining spontaneous daytime GH secretion in the baboon and that one or more catecholamines are involved in the generation of rhythmic GH release.

The aging suppressor klotho: a potential regulator of growth hormone secretion

2014 ◽  
Vol 307 (3) ◽  
pp. E326-E334 ◽  
Author(s):  
Shiri Shahmoon ◽  
Hadara Rubinfeld ◽  
Ido Wolf ◽  
Zvi R. Cohen ◽  
Moshe Hadani ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Secretory Granules ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Negative Regulator ◽  
Prolonged Treatment ◽  
Mrna Levels ◽  
Gh Secretion ◽  
Positive Regulator ◽  
Igf I

Klotho is a transmembranal protein highly expressed in the kidneys, choroid plexus, and anterior pituitary. Klotho can also be cleaved and shed and acts as a circulating hormone. Klotho-deficient mice ( kl/kl mice) develop a phenotype resembling early aging. Several lines of evidence suggest a role for klotho in the regulation of growth hormone (GH) secretion. The kl/kl mice are smaller compared with their wild-type counterparts, and their somatotropes show reduced numbers of secretory granules. Moreover, klotho is a potent inhibitor of the IGF-I pathway, a negative regulator of GH secretion. Therefore, we hypothesized that klotho may enhance GH secretion. The effect of klotho on GH secretion was examined in GH3 rat somatotrophs, cultured rat pituitaries, and cultured human GH-secreting adenomas. In all three models, klotho treatment increased GH secretion. Prolonged treatment of mice with intraperitoneal klotho injections increased mRNA levels of IGF-I and IGF-I-binding protein-3 mRNA in the liver, reflecting increased serum GH levels. In accord with its ability to inhibit the IGF-I pathway, klotho partially restored the inhibitory effect of IGF-I on GH secretion. Klotho is known to be a positive regulator of basic bFGF signaling. We studied rat pituitaries and human adenoma cultures and noted that bFGF increased GH secretion and stimulated ERK1/2 phosphorylation. Both effects were augmented following treatment with klotho. Taken together, our data indicate for the first time that klotho is a positive regulator of GH secretion and suggest the IGF-I and bFGF pathways as potential mediators of this effect.

Effects of repetitive administration of growth hormone-releasing hormone on growth hormone secretion, insulin-like growth factor I, and bone metabolism in postmenopausal women

1989 ◽  
Vol 120 (1) ◽  
pp. 121-128 ◽  
Author(s):  
Paul Franchimont ◽  
Didier Urbain-Choffray ◽  
Pierre Lambelin ◽  
Marie-Anne Fontaine ◽  
Gerard Frangin ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Bone Metabolism ◽  
Postmenopausal Women ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Significant Rise ◽  
Maximum Peak ◽  
Gh Secretion ◽  
Age Related ◽  
Igf I

Abstract. This study sought to determine whether GH response to synthetic GHRH was impaired in 13 postmenopausal (55-71 years) as compared with that in 8 eugonadal women and whether IGF-I and bone metabolism were consequently depressed. Thereafter, the effects of daily iv injections of 80 μg GHRH-44 for 8 days were studied in the same postmenopausal group. In addition to significantly higher basal IGF-I and osteocalcin levels (P< 0.005) in eugonadal as compared with the postmenopausal women, the administration of one GHRH-44 injection resulted in significantly higher 120-min postinjection GH maximum peak and cumulative responses in the former group as well (P< 0.005). Highly significant correlations were observed between 17β-estradiol plasma levels and either GH maximum peak or cumulative responses to GHRH-44 when both groups were pooled together, but not when considered independently. In postmenopausal women, a correlation was found between both age and duration of menopause and GH responses. Repeated GHRH-44 injections in postmenopausal women induced a significant increase in GH response (P< 0.001) as well as in IGF-I levels from day 4 to 8. No phospho-calcium parameters were modified except for a significant rise in osteocalcin from day 2 to 8. These data indicate an age-related loss of sensitivity of somatotrope cells to GHRH-44 in postmenopausal women, partly corrected by repeated daily GHRH-44 injections. As a consequence of the GHRH-induced increase in GH secretion, IGF-I was also enhanced and may be responsible for a stimulatory effect on bone formation, as shown by the osteocalcin increase, uncoupled from bone resorption.

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