scholarly journals The GH-IGF-1 Axis in Circadian Rhythm

2021 ◽  
Vol 14 ◽  
Author(s):  
Weihao Wang ◽  
Xiaoye Duan ◽  
Zhengxiang Huang ◽  
Qi Pan ◽  
Chen Chen ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Circadian Rhythm ◽  
Growth Factor ◽  
Suprachiasmatic Nucleus ◽  
Pulsatile Release ◽  
Regulatory Pathways ◽  
Gh Secretion ◽  
Clock System ◽  
Physiological Adaptations ◽  
Somatostatin Neurons

Organisms have developed common behavioral and physiological adaptations to the influence of the day/night cycle. The CLOCK system forms an internal circadian rhythm in the suprachiasmatic nucleus (SCN) during light/dark input. The SCN may synchronize the growth hormone (GH) secretion rhythm with the dimming cycle through somatostatin neurons, and the change of the clock system may be related to the pulsatile release of GH. The GH—insulin-like growth factor 1 (IGF-1) axis and clock system may interact further on the metabolism through regulatory pathways in peripheral organs. We have summarized the current clinical and animal evidence on the interaction of clock systems with the GH—IGF-1 axis and discussed their effects on metabolism.

Effects of octreotide on insulin-like growth factor I and metabolic indices in growth hormone-treated growth hormone-deficient patients

1993 ◽  
Vol 129 (5) ◽  
pp. 399-408 ◽  
Author(s):  
Torben Laursen ◽  
Jens OL Jorgensen ◽  
Hans Ørskov ◽  
Jens Møller ◽  
Alan G Harris ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Animal Studies ◽  
Area Under The Curve ◽  
Insulin Like Growth Factor ◽  
Gh Secretion ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Igfbp 3

Animal studies have demonstrated that in addition to inhibiting growth hormone (GH) secretion octreotide inhibits in a direct manner hepatic or peripheral insulin-like growth factor I (IGF-I) generation. To test this hypothesis in humans we studied ten GH-deficient patients with frequent blood sampling during 38 h on two occasions. Regular GH therapy was discontinued 72 h prior to each study period. At the start of each study a subcutaneous (sc) injection of GH (3 IU/m2) was given (at 18.00 h). In a single-blinded crossover design, patients received a continuous sc infusion of either octerotide (200 μg/24 h) or placebo (saline). The pharmacokinetics of GH were similar on the two occasions. The area under the curve±sem of serum GH was 142.5±53.6 μg·l−1·h−1 (octreotide) and 144.8±41.8 μg·l−1·h−1 (placebo), (p=0.73); Cmax (μg/l) was 12.5±1.47 (octreotide) and 12.8±1.42 (placebo) (p=0.83), and Tmax (h) was 6.1±0.97 (octreotide) and 5.2±0.65 (placebo) (p=0.49). Growth hormone administration was associated with an increase in serum IGF-I (μg/l), which was identical during the two studies, from 85.3±19.4 to 174.25±30.3 for octreotide and from 97.0±26.4 to 158.8±28.2 for placebo. Mean IGF-I levels (μg/l) were 138.2±25.1 (octreotide) and 134.5±28.6 (placebo) (p=0.78). Similarly, the increase in IGF binding protein 3 (IGFBP-3) levels was identical. Mean IGFBP-3 levels (μg/l) were 2303±323 (octreotide) and 2200±361 (placebo) (p=0.25). Mean insulin levels were significantly lower during octreotide treatment (39.9±17.9 mU/l) than during placebo (59.7±17.8 mU/l) (p<0.05). Mean blood glucose levels were elevated significantly during octreotide infusion (5.98±0.23 mmol/l for octreotide and 5.07±0.16 mmol/l for placebo; p=0.001). Glucagon levels decreased non-significantly (p=0.07) and IGFBP-1 levels tended to increase during infusion of octreotide although not significantly (p=0.41). Levels of the lipid intermediates were identical on the two occasions. Alanine and lactate levels were significantly increased during octreotide infusion. Mean levels of blood alanine (μmol/l) were 470.8±24.2 (octreotide) and 360.1±17.8 (placebo) (p<0.02). Mean levels of blood lactate were 1038±81.0 (octreotide) and 894.4±73.8 (placebo) (p<0.04). We conclude that short-term continuous sc infusion of octreotide has no direct effect on the generation of IGF-I or the pharmacokinetics of exogenous GH in GH-deficient man.

scholarly journals Consensus Statement on the Standardization and Evaluation of Growth Hormone and Insulin-like Growth Factor Assays

2011 ◽  
Vol 57 (4) ◽  
pp. 555-559 ◽  
Author(s):  
David R Clemmons
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Normative Data ◽  
Consensus Statement ◽  
International Workshop ◽  
Research Society ◽  
Insulin Like Growth Factor ◽  
Gh Secretion ◽  
Assay Performance ◽  
Igf I

Abstract Growth hormone (GH) and insulin-like growth factor I (IGF-I) measurements are widely used in the diagnosis of disorders of GH secretion, evaluation of children with short stature from multiple causes, management of disorders that lead to nutritional insufficiency or catabolism, and monitoring both GH and IGF-I replacement therapy. Therefore, there is an ongoing need for accurate and precise measurements of these 2 peptide hormones. Representatives of the Growth Hormone Research Society, the IGF Society, and the IFCC convened an international workshop to review assay standardization, requirements for improving assay comparability, variables that affect assay interpretation, technical factors affecting assay performance, assay validation criteria, and the development and use of normative data. Special attention was given to preanalytical conditions, the use of international commutable reference standards, antibody specificity, matrix requirements, QC analysis, and interference by binding proteins. Recommendations for each of these variables were made for measurements of each peptide. Additionally, specific criteria for IGF-I were recommended for age ranges of normative data, consideration of Tanner staging, and consideration of the effect of body mass index. The consensus statement concludes that major improvements are necessary in the areas of assay performance and comparability. This group recommends that a commutable standard for each assay be implemented for worldwide use and that its recommendations be applied to accomplish the task of providing reliable and clinically useful results.

IGF-I does not affect the net increase in GH release in response to arginine

2002 ◽  
Vol 283 (4) ◽  
pp. E702-E710 ◽  
Author(s):  
Ralf Nass ◽  
Suzan S. Pezzoli ◽  
Ian M. Chapman ◽  
James Patrie ◽  
Raymond L. Hintz ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Young Adults ◽  
Growth Factor ◽  
Negative Feedback ◽  
Random Order ◽  
Feedback Effect ◽  
Insulin Like Growth Factor ◽  
Gh Secretion ◽  
Factor I ◽  
Igf I

Arginine stimulates growth hormone (GH) secretion, possibly by inhibiting hypothalamic somatostatin (SS) release. Insulin-like growth factor I (IGF-I) inhibits GH secretion via effects at the pituitary and/or hypothalamus. We hypothesized that if the dominant action of IGF-I is to suppress GH release at the level of the pituitary, then the arginine-induced net increase in GH concentration would be unaffected by an IGF-I infusion. Eight healthy young adults (3 women, 5 men) were studied on day 2 of a 47-h fast for 12 h (35th-47th h) on four occasions. Saline (Sal) or 10 μg · kg−1 · h−1recombinant human IGF-I was infused intravenously for 5 h from 37 to 42 h of the 47-h fast. Arginine (Arg) (30 g iv) or Sal was infused over 30 min during the IGF-I or Sal infusion from 40 to 40.5 h of the fast. Subjects received the following combinations of treatments in random order: 1) Sal + Sal; 2) Sal + Arg; 3) IGF-I + Sal; 4) IGF-I + Arg. Peak GH concentration on the IGF-I + Arg day was ∼45% of that on the Sal + Arg day. The effect of arginine on net GH release was calculated as [(Sal + Arg) − (Sal + Sal)] − [(IGF-I + Arg) − (IGF-I + Sal)]. There was no significant effect of IGF-I on net arginine-induced GH release over control conditions. These findings suggest that the negative feedback effect of IGF-I on GH secretion is primarily mediated at the pituitary level and/or at the hypothalamus through a mechanism different from the stimulatory effect of arginine.

scholarly journals Increased Orderliness of Growth Hormone (GH) Secretion in GH-Deficient Adults with Low Serum Insulin-Like Growth Factor I

2002 ◽  
Vol 87 (6) ◽  
pp. 2863-2869 ◽  
Author(s):  
Johan Svensson ◽  
Johannes D. Veldhuis ◽  
Ali Iranmanesh ◽  
Bengt-Åke Bengtsson ◽  
Gudmundur Johannsson
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Serum Insulin ◽  
Insulin Like Growth Factor ◽  
Gh Secretion ◽  
Factor I ◽  
Growth Factor I ◽  
Low Serum

Serum Ghrelin Concentrations are Increased in Children With Growth Hormone Insensitivity and Decrease During Long-Term Insulinlike Growth Factor-I Treatment

2008 ◽  
Vol 56 (1) ◽  
pp. 26-31 ◽  
Author(s):  
Aysin Uckun-Kitapci ◽  
Andrea M. Haqq ◽  
Jonathan Q. Purnell ◽  
Kenneth Newcomb ◽  
Hakan Gulkesen ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Normal Control ◽  
Blood Draw ◽  
Gh Secretion ◽  
Factor I ◽  
Insulinlike Growth Factor ◽  
Igf I ◽  
Growth Factor I ◽  
Insulinlike Growth Factor I

BackgroundGhrelin increases food intake, body weight, and growth hormone (GH) secretion. Serum concentrations of ghrelin are low in obese hyperinsulinemic persons, are reduced by infusion of insulin into normal-weight subjects, and are increased in underweight hypoinsulinemic patients with anorexia nervosa. Laron syndrome is an autosomal recessive disorder of GH insensitivity that results in decreased insulinlike growth factor-I (IGF-I) synthesis and growth failure. These patients have elevated GH levels, excess adipose tissue, and are insulin resistant. Because IGF-I has insulinlike actions and patients with GH insensitivity syndrome (GHIS) exhibit excess adiposity, we sought to determine whether ghrelin levels were elevated in these patients and potentially regulated by IGF-I replacement.MethodsThirteen children with GHIS and 20 normal control children matched for age, sex, and body mass index underwent complete physical examination and a fasting blood draw at baseline. The GHIS subjects then underwent follow-up fasting blood draws during therapy with human recombinant IGF-I (80-120 μg/kg, given subcutaneously twice daily). Fasting glucose, insulin, and IGF-I concentrations were measured at the time of collection. Fasting total ghrelin levels were measured on stored serum samples.ResultsThe GHIS subjects had 2-fold higher fasting ghrelin levels (2926 ± 1869 pg/mL) compared with the normal control children (1492 ± 493 pg/mL; P = 0.009), and mean ghrelin values were reduced 56% during 6.4 ± 0.2 years of IGF-I replacement (P < 0.05).ConclusionsGrowth hormone resistance and low IGF-I levels are associated with elevated ghrelin levels, which may potentiate GH secretion and adiposity in these children. Suppression of ghrelin during IGF-I treatment suggests a novel mechanism potentially regulating ghrelin levels.

Antagonist to GH-releasing factor inhibits growth and renal Pi reabsorption in immature rats

1989 ◽  
Vol 257 (1) ◽  
pp. F29-F34 ◽  
Author(s):  
S. E. Mulroney ◽  
M. D. Lumpkin ◽  
A. Haramati
Keyword(s):  
Growth Hormone ◽  
Somatic Growth ◽  
Phosphate Transport ◽  
Adult Rats ◽  
Immature Rat ◽  
Pulsatile Release ◽  
Phosphate Reabsorption ◽  
Gh Secretion ◽  
Immature Rats ◽  
Male Wistar Rats

Compared with adult rats, the immature rat has an enhanced tubular capacity for phosphate reabsorption, which presumably facilitates the growth process. Since the main driving force for growth is thought to be the pulsatile release of growth hormone, we examined the possibility that the adaptation in phosphate handling by the immature kidney is promoted by growth hormone (GH). To address this issue, we used a synthetic peptide antagonist to GH-releasing factor (GRF-AN) that we have shown blocks episodic GH secretion, and attenuates somatic growth. Immature male Wistar rats (4–5 wk of age) were catheterized with Silastic jugular cannulas and placed in metabolic cages. The rats were injected intravenously with either saline or GRF-AN (100 micrograms/kg) twice daily for 4 days. On the 4th day, they were prepared for renal clearance experiments to assess the maximum capacity for phosphate transport (TmPi). In animals treated with GRF-AN, there was an attenuated gain in body weight over 4 days of treatment (5 +/- 2 vs. 23 +/- 2% in saline controls, P less than 0.01). The suppressed growth was associated with a doubling of daily urinary phosphate excretion, and a reduction in the TmPi (3.3 +/- 0.1 vs. 4.6 +/- 0.3 mumol/ml in controls, P less than 0.01). A single injection of the antagonist to a separate group of immature rats did not alter TmPi. Thus injections of this new antagonist to GH-releasing factor over a 4-day period inhibit the pulsatile release of GH and significantly attenuate growth. The decline in growth of the immature rat was associated with a decrease in the renal capacity for phosphate reabsorption, down to levels seen in normal adult rats.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Acetylcholine Modulates the Hormones of the Growth Hormone/Insulinlike Growth Factor-1 Axis During Development in Mice

Endocrinology ◽  
2018 ◽  
Vol 159 (4) ◽  
pp. 1844-1859 ◽  
Author(s):  
Marie-José Lecomte ◽  
Chloé Bertolus ◽  
Nélina Ramanantsoa ◽  
Françoise Saurini ◽  
Jacques Callebert ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Gastrointestinal Hormone ◽  
Stimulatory Action ◽  
Somatotropic Axis ◽  
Newborn Mice ◽  
Gh Secretion ◽  
Insulinlike Growth Factor ◽  
Main Components ◽  
Serum Gh

Abstract Pituitary growth hormone (GH) and insulinlike growth factor (IGF)-1 are anabolic hormones whose physiological roles are particularly important during development. The activity of the GH/IGF-1 axis is controlled by complex neuroendocrine systems including two hypothalamic neuropeptides, GH-releasing hormone (GHRH) and somatostatin (SRIF), and a gastrointestinal hormone, ghrelin. The neurotransmitter acetylcholine (ACh) is involved in tuning GH secretion, and its GH-stimulatory action has mainly been shown in adults but is not clearly documented during development. ACh, together with these hormones and their receptors, is expressed before birth, and somatotroph cells are already responsive to GHRH, SRIF, and ghrelin. We thus hypothesized that ACh could contribute to the modulation of the main components of the somatotropic axis during development. In this study, we generated a choline acetyltransferase knockout mouse line and showed that heterozygous mice display a transient deficit in ACh from embryonic day 18.5 to postnatal day 10, and they recover normal ACh levels from the second postnatal week. This developmental ACh deficiency had no major impact on weight gain and cardiorespiratory status of newborn mice. Using this mouse model, we found that endogenous ACh levels determined the concentrations of circulating GH and IGF-1 at embryonic and postnatal stages. In particular, serum GH level was correlated with brain ACh content. ACh also modulated the levels of GHRH and SRIF in the hypothalamus and ghrelin in the stomach, and it affected the levels of these hormones in the circulation. This study identifies ACh as a potential regulator of the somatotropic axis during the developmental period.

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