Hormone research最新文献

{"title":"Genes of importance in the hormonal regulation of growth plate cartilage.","authors":"Andrei S Chagin,&nbsp;Lars Sävendahl","doi":"10.1159/000192435","DOIUrl":"https://doi.org/10.1159/000192435","url":null,"abstract":"<p><p>Longitudinal bone growth occurs in the growth plate through a process in which resting zone chondrocytes are recruited to start active proliferation and then undergo differentiation, followed by apoptosis and later mineralization. Bone growth is controlled by a multitude of genes encoding for hormones and growth factors acting systemically and/or locally in the growth plate. From studies of individuals with a mutated aromatase gene and a male patient with defective oestrogen receptor (ER) alpha, it has become clear that the action of oestrogen is indispensable for normal pubertal growth and growth plate fusion. As new aromatase inhibitors and specific modulators of ERs are developed, these could offer more specific ways to modulate longitudinal growth and growth plate fusion. It is difficult to extrapolate data obtained in experimental animals, as clear species differences exist, emphasizing the need for new models that will allow studies in human growth plate cartilage.</p>","PeriodicalId":13225,"journal":{"name":"Hormone research","volume":"71 Suppl 2 ","pages":"41-7"},"PeriodicalIF":0.0,"publicationDate":"2009-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000192435","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28145134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress in genome-wide association studies of human height.","authors":"Joel N Hirschhorn,&nbsp;Guillaume Lettre","doi":"10.1159/000192430","DOIUrl":"https://doi.org/10.1159/000192430","url":null,"abstract":"<p><p>Human height (stature) is a strongly genetic trait, with up to 90% of the variation in height within a population determined by a combination of multiple inherited factors. Recent advances in genetics and genomics now permit comprehensive genome-wide surveys of common genetic variations in those variants that are associated with stature. The first such studies have borne fruit, identifying over 40 genetic loci that can be reproducibly shown to have an influence on adult height. These unbiased searches throughout the genome identified several loci that also harbour rare mutations responsible for more severe alterations in height or skeletal growth. Although the predictive value of the common variants thus far discovered remains low, the identification of these loci has led to new insights into the biology of human growth, and may help identify genes that underlie previously uncharacterized syndromes of abnormal skeletal growth.</p>","PeriodicalId":13225,"journal":{"name":"Hormone research","volume":"71 Suppl 2 ","pages":"5-13"},"PeriodicalIF":0.0,"publicationDate":"2009-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000192430","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28145821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetics in growth, and pituitary tumorigenesis. Preface.","authors":"David B Dunger,&nbsp;Vera Popović-Brkić","doi":"10.1159/000192427","DOIUrl":"https://doi.org/10.1159/000192427","url":null,"abstract":"old age ( Hormone Research 2003, vol. 60, suppl. 1). In 2004 and 2005, the Expert Meetings moved to France, first discussing the value of IGF-I in diagnosis and for monitoring the safety and efficacy of GH therapy ( Hormone Research 2004, vol. 62, suppl. 1) and the following year covering methods to determine insulin sensitivity in clinical practice, and the relationship between GH and cognition ( Hormone Research 2005, vol. 64, suppl. 3). The 9th KIGS/KIMS Expert Meeting returned once again to Italy, where participants focused on the relationship between growth and metabolism in skeletal muscle ( Hormone Research 2006, vol. 66, suppl. 1). The 10th KIGS/KIMS Expert Meeting was held in Florence, Italy, in April 2008, and looked at the genetic basis of GH-related diseases. First, genetic approaches to understanding the pathogenesis of growth disorders were discussed, including candidate gene, whole-genome and epigenetic methodology. This was followed by a session looking at the role of genetic changes effecting growth and response to GH therapy. On the second day of the meeting, the genetic basis of pituitary tumorigenesis was the subject of the presentations, covering the full spectrum from animal models to clinical studies. The participants of the 10th KIGS/KIMS Expert Meeting would like to thank Patrick Wilton, Margaretha Lindell, Maria Kołtowska-Häggström and Pfizer Endocrine Care for their ongoing support of this meeting series. The editors would also like to thank the members of the KIGS/ KIMS Strategic Advisory Boards, and the invited experts for their participation and valuable contributions. We hope that this supplement will be of both interest and value to those involved in the treatment of GH deficiency and to the wider clinical and scientific community, and that the organizers will continue to support these meetings in the coming years. David B. Dunger, Cambridge, UK Vera Popović-Brkić, Belgrade, Serbia KIGS (Pfizer International Growth Database) and KIMS (Pfizer International Metabolic Database) are Pfizer’s long-running international databases investigating the effects of growth hormone (GH) therapy on growth and metabolism in children and adults, respectively. The KIGS/KIMS Expert Meetings were established with the same aim as the databases, namely of expanding knowledge in the fields of growth, metabolism and GH therapy. Each meeting provides a forum for debate involving groups of experts with different areas of expertise. Over the years, controversial and less well-known areas have been chosen for debate, allowing a process of consensus formation and standardization of methodology to be attempted. The 1st and 2nd Expert Meetings were held in Italy in 1995 and 1996, before KIMS was initiated, and therefore focused solely on paediatric issues, specifically bone maturation and idiopathic short stature ( Hormone Research 1996, vol. 45, suppl. 2) and the evaluation of body composition in children born small for gestational age ( Hormone","PeriodicalId":13225,"journal":{"name":"Hormone research","volume":"71 Suppl 2 ","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2009-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000192427","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28145819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determinants of short stature and the response to growth hormone therapy.","authors":"David B Dunger","doi":"10.1159/000192428","DOIUrl":"https://doi.org/10.1159/000192428","url":null,"abstract":"genes involved in hypothalamic-pituitary development, but this approach may be limited by fundamental differences between murine and human models of disease. In humans, microscopic chromosomal deletions, duplications and translocations identified in patients with rare developmental hypothalamic-pituitary disorders have shown the importance of other disease genes such as SOCS-2 and SOCS-3 . The application of new techniques in these patient populations, such as comparative genomic hybridization and the detection of submicroscopic chromosomal imbalances, may lead to further identification of disease genes. Professor Dattani pointed out that the recent optimization of high-density whole-genome single-nucleotide polymorphism (SNP) arrays may have the potential to identify many disease genes, thereby revolutionizing the field of human growth genetics. The discovery of gene mutations associated with defective GH secretion or GH responsiveness has been a particularly intense area of study, identifying patients with GH insensitivity due to mutations of the GH receptor and individuals with rare IGF-I gene deletions or IGFI receptor mutations. Ron Rosenfeld reviewed the ways in which analysis of these rare human mutations, combined with murine models, has helped us to clarify the GH cascade and its role in mammalian growth. He pointed out that the major regulator of post-natal growth in mammals is mediated through the stimulation of production of IGF-I, its major circulating IGF-binding protein (IGFBP3) and the acid-labile subunit. The regulation of In April 2008, experts from Europe and the USA gathered in Florence, Italy, to review recent advances in ge n etics and genomics and their potential impact on the diagnosis of growth disorders and response to growth hormone (GH) therapy. The identification of individual gene mutations affecting the GH–insulin-like growth factor (IGF)-I axis through hypothalamic-pituitary development, hypothalamic-pituitary signalling, GH production, GH responsiveness, IGF-I generation and, finally, IGF-I signalling through its receptor has accelerated over the past 20 years. These rare genetic variants have clarified and strengthened our view of the importance of the GH–IGF-I axis in regulating preand post-natal growth, but important questions remain about the overall prevalence of these rare genetic disorders and their relevance to GH therapy. The first part of the expert meeting concentrated on identifying new important gene defects that might increase our understanding and enlarge our list of indications for the GH treatment of growth disorders. The second part focused on the potential of genetics and genomics in refining therapeutic targets and assessing treatment response.","PeriodicalId":13225,"journal":{"name":"Hormone research","volume":"71 Suppl 2 ","pages":"2-4"},"PeriodicalIF":0.0,"publicationDate":"2009-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000192428","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28145820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The candidate gene approach to the diagnosis of monogenic disorders.","authors":"Mehul T Dattani","doi":"10.1159/000192431","DOIUrl":"https://doi.org/10.1159/000192431","url":null,"abstract":"<p><p>The genetic basis of many human diseases has been elucidated by the candidate gene approach. Mouse models of human disease, whether naturally occurring or derived by transgenesis, have enabled a number of disease genes to be identified. Such approaches have formed the basis of the identification of candidate genes implicated in hypothalamo-pituitary development. Nevertheless, significant differences exist between murine and human models of disease. Chromosomal deletions, duplications and translocations that are visible microscopically are also informative and have allowed the discovery of disease genes such as SOX2 and SOX3. In addition, genome-wide mapping techniques using microsatellites have led to the identification of genes such as GPR54, mutations of which are associated with hypogonadotrophic hypogonadism. Newer techniques, such as array comparative genomic hybridization (CGH), have enabled the detection of submicroscopic chromosomal imbalances. These, in turn, can also lead to the identification of disease genes, as has been demonstrated by the discovery of mutations in CHD7 in some patients with the CHARGE syndrome. Most significant, however, is the recent optimization of high-density whole-genome single-nucleotide polymorphism arrays, which provides the potential to identify many disease genes and may revolutionize the field of human genetics.</p>","PeriodicalId":13225,"journal":{"name":"Hormone research","volume":"71 Suppl 2 ","pages":"14-21"},"PeriodicalIF":0.0,"publicationDate":"2009-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000192431","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28145130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The future of research into growth hormone responsiveness.","authors":"Ron G Rosenfeld","doi":"10.1159/000192440","DOIUrl":"https://doi.org/10.1159/000192440","url":null,"abstract":"<p><p>Decades of experience with growth hormone (GH) therapy have indicated considerable variability in responsiveness to therapy, even within single diagnostic categories, such as GH deficiency, Turner syndrome, intrauterine growth retardation and idiopathic short stature. It is likely that the major explanation for such variability lies in the genetic composition of the patient, including mutations of genes participating in the GH-insulin growth factor I cascade and genetic polymorphisms. Future studies of pharmacogenomic and pharmacoproteomic markers may allow us to better predict and categorize responsiveness to therapy.</p>","PeriodicalId":13225,"journal":{"name":"Hormone research","volume":"71 Suppl 2 ","pages":"71-4"},"PeriodicalIF":0.0,"publicationDate":"2009-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000192440","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28217944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pituitary tumour-transforming gene (PTTG) and pituitary senescence.","authors":"Vera Chesnokova,&nbsp;Shlomo Melmed","doi":"10.1159/000192443","DOIUrl":"https://doi.org/10.1159/000192443","url":null,"abstract":"<p><p>Pituitary tumours account for 15% of intracranial neoplasms and are benign monoclonal neoplasms that may be clinically silent or secrete hormones, including prolactin, growth hormone, adrenocorticotrophic hormone or, rarely, thyroid-stimulating hormone or gonadotrophins. These adenomas account for clinical infertility, growth disorders and hypercortisolism or metabolic dysfunctions associated with hypopituitarism. We explored the role of disordered pituitary cell proliferation control in the pathogenesis of these invariably benign adenomas, studying the mechanisms underlying pituitary aneuploidy, premature proliferative arrest (senescence), markers of cell proliferation and tumorigenesis in single, double or triply mutant transgenic mice with mutations of Rb, Pttg and/or p21. Our results provide further insights into the role of cell-cycle control and growth constraints on experimental and human pituitary tumours, which underlie their failure to progress to malignancy. These results improve our understanding of pituitary syndromes associated with infertility, growth disorders, hypercortisolism or adrenal, thyroid and gonadal failure due to abrogated pituitary function.</p>","PeriodicalId":13225,"journal":{"name":"Hormone research","volume":"71 Suppl 2 ","pages":"82-7"},"PeriodicalIF":0.0,"publicationDate":"2009-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000192443","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28217947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The MEN1 gene and pituitary tumours.","authors":"Sunita K Agarwal,&nbsp;Atsushi Ozawa,&nbsp;Carmen M Mateo,&nbsp;Stephen J Marx","doi":"10.1159/000192450","DOIUrl":"https://doi.org/10.1159/000192450","url":null,"abstract":"<p><p>Sporadic multiple endocrine neoplasia type 1 (MEN1) is defined as the occurrence of tumours in two of three main endocrine tissue types: parathyroid, pituitary and pancreaticoduodenal. A prolactinoma variant or Burin variant of MEN1 was found to occur in three large kindreds, with more prolactinomas and fewer gastrinomas than typical MEN1. MEN1 tumours differ from common tumours by showing features from the MEN1 gene (e.g. larger pituitary tumours). They also show various expressions of tumour multiplicity; however, pituitary tumour in MEN1 is usually solitary. Diagnosis in MEN1 carriers during childhood is not directed at cancers but at benign morbid tumours. Morbid prolactinoma occurred at the age of 5 years in one MEN1 individual; hence, this is the earliest age at which to recommend tumour surveillance in carriers. The MEN1 gene shows biallelic inactivation in 30% of some types of common variety endocrine tumours (e.g. parathyroid adenoma, gastrinoma, insulinoma and bronchial carcinoid), but in only 1-5% of common pituitary tumours. Heterozygous knockout of MEN1 in mice provides a robust model of MEN1 and has been found to support further research on anti-angiogenesis therapy for pituitary tumours. The rarity of MEN1 mutations in some MEN1-like states aids the identification of other mutated genes, such as AIP, HRPT2 and p27(Kip1). We present recent clinical and basic findings about the MEN1 gene, particularly concerning hereditary vs. common variety pituitary tumours.</p>","PeriodicalId":13225,"journal":{"name":"Hormone research","volume":"71 Suppl 2 ","pages":"131-8"},"PeriodicalIF":0.0,"publicationDate":"2009-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000192450","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28219744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The growth hormone cascade and its role in mammalian growth.","authors":"Ron G Rosenfeld,&nbsp;Vivian Hwa","doi":"10.1159/000192434","DOIUrl":"https://doi.org/10.1159/000192434","url":null,"abstract":"<p><p>The myriad actions of growth hormone (GH) are still incompletely understood, despite decades of research. Although it is a major regulator of post-natal growth in mammals, much of its effects on skeletal growth are recognized to be mediated indirectly, through the stimulation of production of insulin-like growth factor (IGF)-I, as well as some of the major serum carrier proteins for IGF-I and -II, such as IGF-binding protein-3 (IGFBP-3) and the acid-labile subunit (ALS). The regulation of IGF-I production by GH appears to be mediated entirely by signalling through the Janus kinase (JAK) 2 pathway, via the phosphorylation of the transcription factor, signal transducer and activator of transcription (STAT) 5b. GH also signals, however, through additional pathways that are likely to be critical to the metabolic actions of GH.</p>","PeriodicalId":13225,"journal":{"name":"Hormone research","volume":"71 Suppl 2 ","pages":"36-40"},"PeriodicalIF":0.0,"publicationDate":"2009-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000192434","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28145133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth hormone receptor exon 3 isoforms and their implication in growth disorders and treatment.","authors":"Alexander A L Jorge,&nbsp;Ivo J P Arnhold","doi":"10.1159/000192438","DOIUrl":"https://doi.org/10.1159/000192438","url":null,"abstract":"<p><p>Human recombinant growth hormone (hGH) has been used to treat short stature in several different conditions, but considerable inter-individual variation in short- and long-term growth response exists. Pharmacogenomics can provide important insights into hGH therapy. The GH receptor (GHR) is the first key molecule mediating GH action. In the past 3 years, a common GHR polymorphism reflecting the presence (GHRfl) or absence (GHRd3) of exon 3 has been under intensive investigation regarding its influence on the response to hGH therapy. Studies that evaluated response to GH treatment determined by these two GHR isoforms in children with GH deficiency, girls with Turner syndrome, children born small for gestational age and patients with acromegaly showed that patients carrying the GHRd3 allele demonstrated a greater GH sensitivity than patients homozygous for the GHRfl allele. Other studies presented contradictory data, however, which may be caused by confounding factors such as small sample sizes and differences in experimental design. This GHR exon 3 genotype is the first identified genetic factor found to modulate the individual response to GH therapy. This article reviews the historical aspects and pharmacogenetic studies published to date in relation to this GHR polymorphism. The analyses of present and future validation studies may define the use of this and other polymorphisms in clinical practice, moving from pharmacogenetics to routine application and allowing individualization of hGH doses to optimize final outcome.</p>","PeriodicalId":13225,"journal":{"name":"Hormone research","volume":"71 Suppl 2 ","pages":"55-63"},"PeriodicalIF":0.0,"publicationDate":"2009-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000192438","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28145136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}