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Seminars in Cell & Developmental Biology Jan 2022Sertoli cells (SCs) are immune privileged cells found in the testis that function to immunologically protect maturing germ cells from immune destruction. This immune... (Review)
Review
Sertoli cells (SCs) are immune privileged cells found in the testis that function to immunologically protect maturing germ cells from immune destruction. This immune protection is due to the blood-testis-barrier, which prevents infiltration of cytotoxic immune cells and antibodies, and SC production of immunomodulatory factors, that favor a tolerogenic environment. The ability of SCs to create an immune privileged environment has led to the exploration of their potential use in the treatment of various diseases. SCs have been utilized to create a tolerogenic ectopic microenvironment, to protect co-grafted cells, and to deliver therapeutic proteins through gene therapy. To date, numerous studies have reported the potential use of SCs for the treatment of diabetes, neurodegenerative disorders, and restoration of spermatogenesis. Additionally, SCs have been investigated as a delivery vehicle for therapeutic products to treat other diseases like Laron syndrome, muscular dystrophy, and infections. This review will provide an overview of these therapeutic applications.
Topics: Animals; Cell- and Tissue-Based Therapy; Humans; Male; Mice; Sertoli Cells
PubMed: 33910764
DOI: 10.1016/j.semcdb.2021.04.007 -
Growth Hormone & IGF Research :... Jun 2016
Topics: Adult; Endocrinology; Humans; Insulin-Like Growth Factor I; Laron Syndrome; Recombinant Proteins
PubMed: 26283274
DOI: 10.1016/j.ghir.2015.07.007 -
Orphanet Journal of Rare Diseases Oct 2023Severe primary insulin-like growth factor-I (IGF-I) deficiency (SPIGFD) is a rare growth disorder characterized by short stature (standard deviation score... (Review)
Review
BACKGROUND
Severe primary insulin-like growth factor-I (IGF-I) deficiency (SPIGFD) is a rare growth disorder characterized by short stature (standard deviation score [SDS] ≤ 3.0), low circulating concentrations of IGF-I (SDS ≤ 3.0), and normal or elevated concentrations of growth hormone (GH). Laron syndrome is the best characterized form of SPIGFD, caused by a defect in the GH receptor (GHR) gene. However, awareness of SPIGFD remains low, and individuals living with SPIGFD continue to face challenges associated with diagnosis, treatment and care.
OBJECTIVE
To gather perspectives on the key challenges for individuals and families living with SPIGFD through a multi-stakeholder approach. By highlighting critical gaps in the awareness, diagnosis, and management of SPIGFD, this report aims to provide recommendations to improve care for people affected by SPIGFD globally.
METHODS
An international group of clinical experts, researchers, and patient and caregiver representatives from the SPIGFD community participated in a virtual, half-day meeting to discuss key unmet needs and opportunities to improve the care of people living with SPIGFD.
RESULTS
As a rare disorder, limited awareness and understanding of SPIGFD amongst healthcare professionals (HCPs) poses significant challenges in the diagnosis and treatment of those affected. Patients often face difficulties associated with receiving a formal diagnosis, delayed treatment initiation and limited access to appropriate therapy. This has a considerable impact on the physical health and quality of life for patients, highlighting a need for more education and clearer guidance for HCPs. Support from patient advocacy groups is valuable in helping patients and their families to find appropriate care. However, there remains a need to better understand the burden that SPIGFD has on individuals beyond height, including the impact on physical, emotional, and social wellbeing.
CONCLUSIONS
To address the challenges faced by individuals and families affected by SPIGFD, greater awareness of SPIGFD is needed within the healthcare community, and a consensus on best practice in the care of individuals affected by this condition. Continued efforts are also needed at a global level to challenge existing perceptions around SPIGFD, and identify solutions that promote equitable access to appropriate care. Medical writing support was industry-sponsored.
Topics: Humans; Insulin-Like Growth Factor I; Quality of Life; Laron Syndrome; Dwarfism; Growth Disorders
PubMed: 37805563
DOI: 10.1186/s13023-023-02928-7 -
AJNR. American Journal of Neuroradiology Sep 2011Patients with LS have an inborn growth hormone resistance, resulting in failure to generate IGF-1. The purpose of this study was to evaluate the size of the eye and...
BACKGROUND AND PURPOSE
Patients with LS have an inborn growth hormone resistance, resulting in failure to generate IGF-1. The purpose of this study was to evaluate the size of the eye and orbit in LS.
MATERIALS AND METHODS
We retrospectively reviewed the MR imaging of the brain in 9 patients with LS for the following parameters: axial diameter of the globe, interzygomatic distance, perpendicular distance from the interzygomatic line to margins of the globe, medial-to-lateral diameter of the orbit at the anterior orbital rim, distance from the anterior orbital rim to the anterior globe, maximal distance between the medial walls of the orbits, lateral orbital wall angle, lateral orbital wall length, and mediolateral thickness of the intraorbital fat in the most cranial image of the orbit. All measurements were made bilaterally. Twenty patients referred for MR imaging for unrelated reasons served as control subjects.
RESULTS
Compared with the control group, the patients with LS had a significantly smaller maximal globe diameter and shallower but wider orbits due to a shorter lateral wall, a smaller medial distance between the orbits, and a larger angle of the orbit. The ratio between the most anterior orbital diameter and the globe was greater than that in controls. The position of the globe was more anterior in relation to the interzygomatic line.
CONCLUSIONS
Shallow and wide orbits and small globes relative to orbital size are seen in LS and may be secondary to IGF-1 deficiency.
Topics: Adult; Aged; Eye; Female; Humans; Laron Syndrome; Male; Middle Aged; Orbit; Organ Size; Retrospective Studies
PubMed: 21757529
DOI: 10.3174/ajnr.A2573 -
Obesity Research & Clinical Practice Mar 2009To study the metabolic parameters which may affect the excessive weight of treated and untreated patients with Laron Syndrome.
OBJECTIVE
To study the metabolic parameters which may affect the excessive weight of treated and untreated patients with Laron Syndrome.
DESIGN
Body composition, daily caloric intake and resting energy expenditure (REE), when possible, were measured for each patient. Caloric intake was calculated based on 7-day food records, REE was measured by indirect calorimetry and body composition was determined by dual energy X-ray absorptiometry (DEXA).
SUBJECTS
Nine untreated adult subjects with Laron Syndrome (6 female subjects, 3 male subjects) aged 28-53 years and 4 girls with Laron Syndrome treated by insulin-like growth factor-I (IGF-I) 120-150 μg/kg/d were included in the study.
RESULTS
Patients with Laron Syndrome have an abnormally high body fat (BF) mass (54 ± 10% of body weight) and a relatively low lean body mass (LBM) compared to a healthy normal population. Energy intake varied but in most of the patients was not significantly higher than the measured REE. The REE corrected for LBM was higher than expected, based on our norms for healthy adults. The mean distribution of energy sources in the food was 47% carbohydrates, 17% protein and 36% fat.
CONCLUSION
The severe obesity of patients with Laron Syndrome is not due to hyperphagia or hypometabolism.
PubMed: 24345535
DOI: 10.1016/j.orcp.2008.11.001 -
International Journal of Molecular... May 2018Growth hormone (GH) promotes body growth by binding with two GH receptors (GHRs) at the cell surface. GHRs interact with Janus kinase, signal transducers, and... (Review)
Review
Growth hormone (GH) promotes body growth by binding with two GH receptors (GHRs) at the cell surface. GHRs interact with Janus kinase, signal transducers, and transcription activators to stimulate metabolic effects and insulin-like growth factor (IGF) synthesis. However, process dysfunctions in the GH⁻GHR⁻IGF-1 axis cause animal dwarfism. If, during the GH process, GHR is not successfully recognized and/or bound, or GHR fails to transmit the GH signal to IGF-1, the GH dysfunction occurs. The goal of this review was to focus on the GHR mutations that lead to failures in the GH⁻GHR⁻IGF-1 signal transaction process in the dwarf phenotype. Until now, more than 90 GHR mutations relevant to human short stature (Laron syndrome and idiopathic short stature), including deletions, missense, nonsense, frameshift, and splice site mutations, and four GHR defects associated with chicken dwarfism, have been described. Among the 93 identified mutations of human GHR, 68 occur extracellularly, 13 occur in GHR introns, 10 occur intracellularly, and two occur in the transmembrane. These mutations interfere with the interaction between GH and GHRs, GHR dimerization, downstream signaling, and the expression of GHR. These mutations cause aberrant functioning in the GH-GHR-IGF-1 axis, resulting in defects in the number and diameter of muscle fibers as well as bone development.
Topics: Animals; Dwarfism; Gene Expression Regulation; Growth Hormone; Humans; Insulin-Like Growth Factor I; Laron Syndrome; Mutation; Receptors, Somatotropin; Signal Transduction
PubMed: 29748515
DOI: 10.3390/ijms19051433 -
Journal of Pediatric Endocrinology &... Apr 1999A description of the clinical, biochemical and endocrinological features of the classical form of the syndrome of primary growth hormone (GH) resistance (Laron syndrome)... (Review)
Review
A description of the clinical, biochemical and endocrinological features of the classical form of the syndrome of primary growth hormone (GH) resistance (Laron syndrome) is presented including the progressive changes during follow-up from infancy into adulthood. The main diagnostic features are: severe growth retardation, acromicria, small gonads and genitalia, and obesity. Serum GH levels are elevated and insulin-like growth factor-I (IGF-I) values are low and do not rise upon stimulation by exogenous hGH. The pathogenesis of this syndrome is due to various molecular defects from exon deletion to nonsense, frameshift, splice and missense mutations in the GH receptor (GH-R) gene or in its post-receptor pathways.
Topics: Abnormalities, Multiple; Carrier Proteins; Drug Resistance; Endocrine System; Female; Growth Disorders; Human Growth Hormone; Humans; Male; Musculoskeletal Abnormalities; Receptors, Somatotropin; Sexual Maturation; Syndrome
PubMed: 10698588
DOI: No ID Found -
Growth Hormone & IGF Research :... Jun 2016A growth hormone (GH) dependent substance responsible for sulfate uptake by costal cartilage of hypophysectomized rats, labeled sulfation factor, was reported in 1957....
UNLABELLED
A growth hormone (GH) dependent substance responsible for sulfate uptake by costal cartilage of hypophysectomized rats, labeled sulfation factor, was reported in 1957. In 1962 the radioimmunoassay for GH was described. The clinical picture of severe GH deficiency but with high serum concentrations of GH was reported in 3 siblings in 1966 and followed by a 1968 report of 22 patients belonging to 14 consanguineous oriental Jewish families in Israel. Defective sulfation factor generation was demonstrated in 15 of these individuals and in a 1971 report; FFA response to IV GH and growth response to GH injections suggested competitive saturation of peripheral tissue receptors by an abnormal GH. However, studies published in 1973 demonstrated normal fractionation of their circulating GH, and normal binding of GH from 22 patients to various antisera used for radioimmunoassay. In 1976, the Israeli investigators reported that circulating GH from 7 patients reacted normally in the recently developed radioreceptor assay for GH. In 1984, using hepatic microsome pellets, they demonstrated that the defect was a failure of GH binding to receptors. Characterization of the human GH receptor (GHR) gene, reported in 1989, included the initial description of a genetic defect of the GHR in 2 of 9 Israeli patients. At about the same time began the identification in Ecuador of what was to become the largest population of GH insensitivity in the world, ~100 individuals, and the only substantial population with a common mutation of the GH receptor. Treatment studies with recombinant IGF-I began in 1990. Growth response was modest compared to that of GH treated GH deficient subjects. The spectrum of GH insensitivity has expanded beyond GH receptor deficiency to include postreceptor abnormalities: IGF-I gene mutation (1996); IGF-I receptor mutation (2003); signal transducer and activator of transcription 5b mutation (2003); and mutation of the GH-dependent acid labile subunit (2004).
CONCLUSION
Rare conditions of GH insensitivity caused by GH receptor and postreceptor abnormalities have provided insights into the processes of growth, body composition, and metabolism.
Topics: Ecuador; History, 20th Century; History, 21st Century; Humans; Insulin-Like Growth Factor I; Laron Syndrome; Obesity; Receptor, IGF Type 1; Receptors, Somatotropin; Recombinant Proteins; STAT5 Transcription Factor
PubMed: 26276451
DOI: 10.1016/j.ghir.2015.08.001 -
Acta Paediatrica (Oslo, Norway : 1992).... Sep 1992
Review
Topics: Dwarfism; Humans; Insulin-Like Growth Factor I; Receptors, Somatotropin; Syndrome
PubMed: 1458005
DOI: No ID Found -
Gene Oct 2013The fossil remains of Homo floresiensis have been debated extensively over the past few years. This paper gives a review of the various pathologies ascribed to LB1, the... (Review)
Review
The fossil remains of Homo floresiensis have been debated extensively over the past few years. This paper gives a review of the various pathologies ascribed to LB1, the type specimen of H. floresiensis, and associated individuals. This paper will assess the arguments for growth anomalies, microcephaly, Laron syndrome and cretinism. Additionally, some of the analyses done by proponents of the pathology theory will be methodologically evaluated. Subsequently, a brief overview of the alternative hypotheses regarding the origin of H. floresiensis will be given.
Topics: Animals; Fossils; Hominidae; Humans; Mandible; Microcephaly; Skull
PubMed: 23792064
DOI: 10.1016/j.gene.2013.06.010