Treatment With Recombinant Igf-I for Patients With Growth Hormone (Gh) Gene Deletions. 37

Abstract. Some patients with active acromegaly have elevated plasma IGF-I concentrations with only minimal elevation of plasma GH. We compared adenomatous GH and SRIH expression in 3 such patients (patients No. 1, 2 and 3; basal plasma GH level < 4 μg/l) and in 3 acromegalic patients with high basal plasma GH level (patients No. 4, 5 and 6; 51.7 ± 16.1 μg/l, mean ± sem). By immunocytochemistry, all the tumours proved to be somatotropic adenomas. At the ultrastructural level, signs of low secretory activity were observed in adenomas from patients No. 2 and 3. Perifused adenoma cells of patients No. 1, 2 and 3 released very little GH compared with those of patients No. 4, 5 and 6 (1± 0.37 vs 51.5± 34.1 μg · (10−6 cells) · min−1, p< 0.001). Adenoma SRIH content was 65.7 and 30.6 pg/mg proteins in patients No. 1 and 2, whereas it was undetectable in the others (patients No. 4, 5 and 6). Northern blot analysis showed that the GH gene was poorly expressed in the adenomas from patients No. 1, 2 and 3 compared with the adenomas from patients No. 4, 5 and 6. SRIH mRNA was detected in all 6 adenomas. However, the signal was more intense in the adenomas from patients No. 1, 2 and 3 than in those from patients No. 4, 5 and 6. In conclusion, because of the variability of the biosynthetic and secretory potential of the somatotropic adenomas, patients harbouring this type of pituitary tumours can exhibit a wide range of plasma GH levels. In acromegaly with minimal elevation of plasma GH, the synthesis of SRIH by the adenoma cells themselves could play a role in the inhibition of GH expression.

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Neuroendocrine regulation of growth hormone

Acta Endocrinologica ◽

10.1530/eje.0.1320012 ◽

1995 ◽

Vol 132 (1) ◽

pp. 12-24 ◽

Cited By ~ 111

Author(s):

Jérôme Bertherat ◽

Marie Thérèse Bluet-Pajot ◽

Jacques Epelbaum

Keyword(s):

Gene Expression ◽

Growth Hormone ◽

Short Review ◽

Neuroendocrine Regulation ◽

Transcriptional Level ◽

Igf I ◽

Gh Gene ◽

Differentiation And Proliferation ◽

Extrahypothalamic Neurons ◽

Regulation Of Growth

Bertherat J, Bluet-Pajot MT, Epelbaum J. Neuroendocrine regulation of growth hormone. Eur J Endocrinol 1995;132:12–24. ISSN 0804–4643 This short review is focused on the neuroendocrine regulation of growth hormone (GH) pulsatile secretory pattern and GH gene expression. The neuronal network involved in the central control of GH includes extrahypothalamic neurons such as the noradrenergic and cholinergic systems, which regulate the two antagonistic neurohormonal systems: somatostatin (SRIH) and GH-releasing hormone (GHRH). Intrahypothalamic Proopiomelanocortin- and Galanin-containing interneurons also participate in the regulation of SRIH and GHRH neuronal activity, which also is dependent on sex steroids and GH and/or insulin-like growth factor I (IGF-I) feedback. cAMP (controlled mainly by GHRH and SRIH), thyroid and glucocorticoid hormones, IGF-I and activin are among the factors that regulate GH gene expression at the transcriptional level and may play a role in somatotroph differentiation and proliferation during ontogeny as well as physiological and pathological states such as acromegaly. J Epelbaum, U159 INSERM, Centre Paul Broca, 2 ter rue d'Alésia, 75014 Paris, France

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Laron syndrome – A case Report

JMS SKIMS ◽

10.33883/jms.v20i2.204 ◽

2017 ◽

Vol 20 (2) ◽

pp. 104-106

Author(s):

Javaid Ahmad Bhat ◽

Moomin Hussain Bhat ◽

Hilal Bhat ◽

Mona Sood ◽

Shariq Rashid Masoodi

Keyword(s):

Growth Hormone ◽

Case Report ◽

Hormone Receptor ◽

Growth Hormone Receptor ◽

Genetic Disorder ◽

Female Child ◽

Receptor Signaling ◽

Laron Syndrome ◽

Rare Genetic Disorder ◽

Igf I

Background : Laron & colleagues (1966) reported a rare genetic disorder in Israliei Jewish sublings which was characterized by insensitivity to growth hormone due to abnormality in growth hormone receptor or post receptor signaling pathway.Case Report: We hereby report a case of a 5 year old female child who presented to us with features similar to Laron syndrome. The diagnosis was made & confirmed by various Lab. investigations like low IGF-I levels and managed accordingly. JMS 2017; 20 (2):104-106

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Biomarkers of Acromegaly and Growth Hormone Action

Protein and Peptide Letters ◽

10.2174/0929866527666200420103816 ◽

2020 ◽

Vol 27 (12) ◽

pp. 1231-1245

Author(s):

Filippo Maffezzoni ◽

Teresa Porcelli ◽

Andrea Delbarba ◽

Letizia Pezzaioli ◽

Carlo Cappelli ◽

...

Keyword(s):

Growth Hormone ◽

Biological Markers ◽

Clinical Care ◽

Hormone Deficiency ◽

Surrogate Outcomes ◽

Current State ◽

Growth Hormone Action ◽

Igf I ◽

Definition Of

: Biological markers (biomarkers) play a key role in drug development, regulatory approval and clinical care of patients and are linked to clinical and surrogate outcomes. : Both acromegaly and Growth Hormone Deficiency (GHD) are pathological conditions related to important comorbidities that, in addition to having stringent diagnostic criteria, require valid markers for the definition of treatment, treatment monitoring and follow-up. GH and insulin-like growth factor-I (IGF-I) are the main biomarkers of GH action in children and adults while, in acromegaly, both GH and IGF-I are established biomarkers of disease activity. : However, although GH and IGF-I are widely validated biomarkers of GHD and acromegaly, their role is not completely exhaustive or suitable for clinical classification and follow-up. Therefore, new biological markers for acromegaly and GH replacement therapy are strongly needed. : The aim of this paper is to review and summarize the current state in the field pointing out new potential biomarkers for acromegaly and GH use/abuse.

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Differential Diagnosis of the Short IGF-I-Deficient Child with Apparently Normal Growth Hormone Secretion

Hormone Research in Paediatrics ◽

10.1159/000516407 ◽

2021 ◽

pp. 1-24

Author(s):

Jan M. Wit ◽

Sjoerd D. Joustra ◽

Monique Losekoot ◽

Hermine A. van Duyvenvoorde ◽

Christiaan de Bruin

Keyword(s):

Growth Hormone ◽

Differential Diagnosis ◽

Growth Hormone Secretion ◽

Normal Growth ◽

Stimulation Test ◽

Healthy Children ◽

Genetic Causes ◽

Gh Secretion ◽

Igf I

The current differential diagnosis for a short child with low insulin-like growth factor I (IGF-I) and a normal growth hormone (GH) peak in a GH stimulation test (GHST), after exclusion of acquired causes, includes the following disorders: (1) a decreased spontaneous GH secretion in contrast to a normal stimulated GH peak (“GH neurosecretory dysfunction,” GHND) and (2) genetic conditions with a normal GH sensitivity (e.g., pathogenic variants of GH1 or GHSR) and (3) GH insensitivity (GHI). We present a critical appraisal of the concept of GHND and the role of 12- or 24-h GH profiles in the selection of children for GH treatment. The mean 24-h GH concentration in healthy children overlaps with that in those with GH deficiency, indicating that the previously proposed cutoff limit (3.0–3.2 μg/L) is too high. The main advantage of performing a GH profile is that it prevents about 20% of false-positive test results of the GHST, while it also detects a low spontaneous GH secretion in children who would be considered GH sufficient based on a stimulation test. However, due to a considerable burden for patients and the health budget, GH profiles are only used in few centres. Regarding genetic causes, there is good evidence of the existence of Kowarski syndrome (due to GH1 variants) but less on the role of GHSR variants. Several genetic causes of (partial) GHI are known (GHR, STAT5B, STAT3, IGF1, IGFALS defects, and Noonan and 3M syndromes), some responding positively to GH therapy. In the final section, we speculate on hypothetical causes.

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Regulation of GH and GH Signaling by Nutrients

Cells ◽

10.3390/cells10061376 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1376

Author(s):

Marina Caputo ◽

Stella Pigni ◽

Emanuela Agosti ◽

Tommaso Daffara ◽

Alice Ferrero ◽

...

Keyword(s):

Growth Hormone ◽

Insulin Signaling ◽

Current Knowledge ◽

Nutrient Sensing ◽

Feedback Mechanisms ◽

Nutrition Management ◽

Prevention And Treatment ◽

Igf I ◽

Macro And Micronutrients ◽

Energy Deprivation

Growth hormone (GH) and insulin-like growth factor-1 (IGF-I) are pleiotropic hormones with important roles in lifespan. They promote growth, anabolic actions, and body maintenance, and in conditions of energy deprivation, favor catabolic feedback mechanisms switching from carbohydrate oxidation to lipolysis, with the aim to preserve protein storages and survival. IGF-I/insulin signaling was also the first one identified in the regulation of lifespan in relation to the nutrient-sensing. Indeed, nutrients are crucial modifiers of the GH/IGF-I axis, and these hormones also regulate the complex orchestration of utilization of nutrients in cell and tissues. The aim of this review is to summarize current knowledge on the reciprocal feedback among the GH/IGF-I axis, macro and micronutrients, and dietary regimens, including caloric restriction. Expanding the depth of information on this topic could open perspectives in nutrition management, prevention, and treatment of GH/IGF-I deficiency or excess during life.

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