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.

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.

Pulsatile growth hormone secretion, circulating insulin-like growth factor-1 concentration and cellular density of somatotrophs differ between Wagyu and Holstein steers

2001 ◽  
Vol 73 (3) ◽  
pp. 425-432 ◽  
Author(s):  
M. Matsuzaki ◽  
T. Sato ◽  
S. Morita ◽  
N. Shiba ◽  
E. Tsuneishi ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Plasma Levels ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Insulin Like Growth Factor ◽  
Marbling Score ◽  
Somatotropic Axis ◽  
Gh Secretion ◽  
Cellular Density

AbstractJapanese Black cattle (Wagyu), deposit much higher amounts of intramuscular fat, known as marbling, than other breeds of cattle. To determine whether this unique fat deposition is attributable to the somatotropic axis, we compared pulsatile growth hormone (GH) secretion, plasma levels of insulin-like growth factor-1 (IGF-1) and cellular density of somatotrophs (GH-expressing cells) in the anterior pituitary glands of Japanese Black and Holstein steers. Blood samples were withdrawn every 15 min for 6 h from 14 Japanese Black and 12 Holstein steers at about 17 months of age, and GH and IGF-1 concentrations were determined. The distribution and proportion of GH-expressing cells were analysed by immunohistochemistry combined with point-count morphometry in pituitaries from six steers from each breed aged about 18 to 21 months. Overall mean and baseline plasma GH concentrations were lower (P < 0·001) in Japanese Black than Holstein steers. In addition, Japanese Black had smaller (P < 0·05) amplitudes of GH secretory pulses than Holstein steers, whereas the GH pulse frequency did not differ between the breeds. Japanese Black steers also had lower (P < 0·001) plasma levels of IGF-1 than Holstein steers. The marbling score of Japanese Black steers was higher (P < 0·001) than that of Holsteins at the same carcass weight. The proportion of GH-expressing cells was smaller (P < 0·05) in Japanese Black than Holstein steers at the hind dorsal and hind ventral regions of the adenohypophysis. Thus, in Japanese Black and Holstein steers, the breed difference in the relative density of GH-expressing cells corresponded to that in profiles of pulsatile GH secretion. These results suggest that the features of the somatotropic axis intrinsically differ between Japanese Black and Holstein cattle and that these features may be partly responsible for the genetic ability of the former to deposit greater amounts of marbling fat and for the smaller frame of Wagyu cattle.

Lack of growth hormone effect on insulin-associated suppression of insulinlike growth factor binding protein 1 in humans

Diabetes ◽  
1990 ◽  
Vol 39 (10) ◽  
pp. 1251-1256 ◽  
Author(s):  
C. A. Conover ◽  
P. C. Butler ◽  
M. Wang ◽  
R. A. Rizza ◽  
P. D. Lee
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Binding Protein ◽  
Factor Binding ◽  
Insulinlike Growth Factor ◽  
Hormone Effect

Effects of refeeding of undernourished and insulin treatment of diabetic neonatal rats on IGF and IGFBP

1996 ◽  
Vol 271 (2) ◽  
pp. E223-E231 ◽  
Author(s):  
L. Goya ◽  
F. Rivero ◽  
M. A. Martin ◽  
R. Arahuetes ◽  
E. R. Hernandez ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Growth Factor ◽  
Mrna Expression ◽  
Insulin Treatment ◽  
Diabetic Rats ◽  
Insulin Like Growth Factor ◽  
Neonatal Rats ◽  
Igf I ◽  
Serum Gh

The effect of refeeding and insulin treatment of undernourished and diabetic neonatal rats, respectively, on the regulation of insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) was investigated. The changes in body weight, insulinemia, glycemia, serum IGF-I, and growth hormone (GH) as well as the increase of the 30-kDa IGFBP in undernourished and diabetic neonatal rats previously shown elsewhere were reversed by refeeding and insulin treatment, respectively. Also, changes in liver mRNA expression of IGF-I and-II and IGFBP-1 and -2 were restored in refed undernourished and IGF-I and IGFBP-1 levels recovered in insulin-treated diabetic rats. However, serum GH was still below normal after rehabilitation in both situations. Thus the present results support the idea of a GH-independent IGF/ IGFBP regulation mediated by a balance of insulin and nutrients as has already been suggested in previous neonatal studies.

Is there a place for urinary growth hormone measurement?

1993 ◽  
Vol 128 (3) ◽  
pp. 197-201 ◽  
Author(s):  
Maria N Moreira-Andrés ◽  
Francisco J Cañizo ◽  
Federico Hawkins
Keyword(s):  
Growth Hormone ◽  
Screening Method ◽  
Small Sample ◽  
Point Of View ◽  
Intrasubject Variability ◽  
Gh Secretion ◽  
Lack Of Information ◽  
Low Levels ◽  
Plasma Gh ◽  
Serum Gh

The evaluation of growth hormone (GH) secretion is an important problem in pediatric endocrine practice. The diagnosis of GH insufficiency is based on the finding of a "blunted" GH response to GH provocative tests or on the demonstration of a decreased endogenous secretion. From a practical point of view, these methods are uncomfortable, expensive and time consuming. Recently, very sensitive specific assays to measure human GH in urine have been developed. We present a discussion of available data on these tests in order to estimate their role in the evaluation of a short or slowly growing child. The present available assays allow measuring very low levels of GH in a small sample of untreated urine. The main limitations of urinary GH measurement are the intrasubject variability, wide normal range, overlapping results in several GH secretory states and lack of information on GH pulsatility. However, most of these limitations also apply to other tests of GH secretion. The advantage of urinary GH tests is that they provide, in an easy procedure, information on serum GH concentration. There is good correlation between urinary and serum GH concentration and several findings suggest that urinary GH excretion reflects changes in plasma GH levels during the period of urine collection. Therefore, the usefulness of urinary GH measurement is that of a simpler and cheaper screening method for assessing integrated serum GH concentration in clinical practice.

scholarly journals Somatotropic Axis and Obesity: Is There Any Role for the Mediterranean Diet?

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2228 ◽  
Author(s):  
Giovanna Muscogiuri ◽  
Luigi Barrea ◽  
Daniela Laudisio ◽  
Carolina Di Somma ◽  
Gabriella Pugliese ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Growth Hormone ◽  
Growth Factor ◽  
Mediterranean Diet ◽  
Adult Women ◽  
Model Assessment ◽  
Insulin Like Growth Factor ◽  
Somatotropic Axis ◽  
Peak Response ◽  
The Mediterranean

Obesity is associated with reduced spontaneous and stimulated growth hormone (GH) secretion and basal insulin-like growth factor I (IGF-1) levels—which in turn is associated with increased prevalence of cardiovascular risk factors. The aim of this study was to investigate: (1) the association of somatotropic axis with cardiometabolic status; (2) the association of somatotropic axis with the Mediterranean diet and nutritional pattern in people with obesity. Cross-sectional observational study was carried out in 200 adult women, aged 36.98 ± 11.10 years with severe obesity (body mass index—BMI of 45.19 ± 6.30 kg/m2). The adherence to the Mediterranean diet and the total calorie intake was assessed. Anthropometric measurements, body composition and biochemical profile were determined along with Growth Hormone (GH)/Insulin like Growth Factor 1 (IGF-1) axis and insulin resistance (homeostatic model assessment for insulin resistance—HoMA-IR). The enrolled subjects were compared after being divided according to GH peak response and according to IGF-1 standard deviation scores (SDS). Derangements of GH peak were detected in 61.5% of studied patients while IGF-1 deficiency was detected in 71% of the population. Both blunted GH peak response and IGF-1 SDS were indicators of derangements of somatotropic axis and were associated with comparable results in terms of cardiometabolic sequelae. Both GH peak and IGF-1 levels were inversely associated with anthropometric and metabolic parameters. The adherence to the Mediterranean diet predicts GH peak response. Fatty liver index (FLI), fat mass (FM) and phase angle (PhA) were predictive factors of GH peak response as well. In conclusion derangements of somatotropic axis is associated with a worse cardiometabolic profile in people with obesity. A high adherence to the Mediterranean diet—and in particular protein intake—was associated with a better GH status.

scholarly journals 17α-Estradiol Modulates IGF1 and Hepatic Gene Expression in a Sex-Specific Manner

2020 ◽  
Author(s):  
Silvana Sidhom ◽  
Augusto Schneider ◽  
Yimin Fang ◽  
Samuel McFadden ◽  
Justin Darcy ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Insulin Sensitivity ◽  
Growth Hormone Receptor ◽  
Health Benefits ◽  
Male Mice ◽  
Wild Type ◽  
Somatotropic Axis ◽  
Gh Secretion ◽  
17Β Estradiol ◽  
Estradiol 17Β

Abstract Aging is the greatest risk factor for most chronic diseases. The somatotropic axis is one of the most conserved biological pathways that regulates aging across species. 17α-Estradiol (17α-E2), a diastereomer of 17β-estradiol (17β-E2), was recently found to elicit health benefits, including improved insulin sensitivity and extend longevity exclusively in male mice. Given that 17β-E2 is known to modulate somatotropic signaling in females through actions in the pituitary and liver, we hypothesized that 17α-E2 may be modulating the somatotropic axis in males, thereby contributing to health benefits. Herein, we demonstrate that 17α-E2 increases hepatic insulin-like growth factor 1 (IGF1) production in male mice without inducing any changes in pulsatile growth hormone (GH) secretion. Using growth hormone receptor knockout (GHRKO) mice, we subsequently determined that the induction of hepatic IGF1 by 17α-E2 is dependent upon GH signaling in male mice, and that 17α-E2 elicits no effects on IGF1 production in female mice. We also determined that 17α-E2 failed to feminize the hepatic transcriptional profile in normal (N) male mice, as evidenced by a clear divergence between the sexes, regardless of treatment. Conversely, significant overlap in transcriptional profiles was observed between sexes in GHRKO mice, and this was unaffected by 17α-E2 treatment. Based on these findings, we propose that 17α-E2 acts as a pleiotropic pathway modulator in male mice by uncoupling IGF1 production from insulin sensitivity. In summary, 17α-E2 treatment upregulates IGF1 production in wild-type (and N) male mice in what appears to be a GH-dependent fashion, while no effects in female IGF1 production are observed following 17α-E2 treatment.

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.

Dental Development in Children with Growth Hormone Insensitivity Syndrome: Demirjian Analysis of Serial Panoramic Radiographs

2009 ◽  
Vol 46 (4) ◽  
pp. 409-414 ◽  
Author(s):  
Richard Campbell ◽  
Randy Weinshel ◽  
Philippe Backeljauw ◽  
Stephen Wilson ◽  
Judy Bean ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Tooth Development ◽  
Dental Development ◽  
Panoramic Radiographs ◽  
Factor I ◽  
Insulinlike Growth Factor ◽  
Growth Hormone Insensitivity ◽  
Growth Factor I ◽  
Insulinlike Growth Factor I

Objective: This study evaluates the effects of 8 years of insulinlike growth factor-I therapy on tooth development in patients with growth hormone insensitivity syndrome. Methods: Forty-nine panoramic radiographs were evaluated from eight patients (six boys, two girls). Seven teeth in the mandibular left region were graded according to the Demirjian system. Radiographs were taken at the start of insulinlike growth factor-I therapy and were continued at approximately yearly intervals for 8 years. Results: Three of six boys and one of two girls who began treatment with insulinlike growth factor-I at earlier ages experienced an increase in the rate of tooth development. One of six boys who began treatment with insulinlike growth factor-I at a later age had a slower rate of dental development. The patients had more rapid tooth maturation during the beginning of treatment. By the end of treatment, all patients had normal dental maturity for their age. Conclusions: Treatment of growth hormone insensitivity syndrome with insulinlike growth factor-I appears to lead to an increase in dental maturation, particularly in younger patients. After 8 years all patients had achieved normal dental development.

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