A5025381333- Growth Hormone and Insulin-like Growth Factors
- Pharmacogenetics and Drug Metabolism
- Osteoarthritis Treatment and Mechanisms
- Hormonal Regulation and Hypertension
- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- TGF-β signaling in diseases
- Connective tissue disorders research
- Hormonal and reproductive studies
- Bone Metabolism and Diseases
- Sexual Differentiation and Disorders
- Adipose Tissue and Metabolism
- Estrogen and related hormone effects
- Birth, Development, and Health
- Fibroblast Growth Factor Research
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Parathyroid Disorders and Treatments
- Hypothalamic control of reproductive hormones
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Bone health and osteoporosis research
- Drug Transport and Resistance Mechanisms
- Cancer, Hypoxia, and Metabolism
- Neonatal Health and Biochemistry
- Proteoglycans and glycosaminoglycans research
National Institutes of Health
2015-2024
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2014-2023
Foundation for Growth Science
2016
Eunice Kennedy Shriver Center
2016
University of North Carolina at Chapel Hill
2015
Institut thématique Génétique, génomique et bioinformatique
2011
United States Public Health Service
1994-2006
Health and Human Development (2HD) Research Network
1995-2005
Institute of Developmental Physiology
2005
Leiden University Medical Center
2005
We hypothesized that estradiol levels are higher in prepubertal girls than boys and this greater secretion of might drive the more rapid epiphyseal development earlier puberty girls. Since previous assays have lacked adequate sensitivity to test hypothesis girls, we developed a new ultrasensitive assay measure estrogen levels. The uses strain Saccharomyces cerevisiae genetically engineered for extreme estrogen. Yeast were transformed with plasmids encoding human receptor an...
Estrogen is critical for epiphyseal fusion in both young men and women. In this study, we explored the cellular mechanisms by which estrogen causes phenomenon. Juvenile ovariectomized female rabbits received either 70 microg/kg estradiol cypionate or vehicle i.m. once a week. Growth plates from proximal tibia, distal femur were analyzed after 2, 4, 6, 8 weeks of treatment. vehicle-treated animals, there was gradual senescent decline tibial growth rate, rate chondrocyte proliferation, plate...
In mammals, growth of long bones occurs at the plate, a cartilage structure that contains three principal layers: resting, proliferative, and hypertrophic zones. The function resting zone is not well understood. We removed proliferative zones from rabbit distal ulnar plate in vivo, leaving only zone. Within 1 wk, complete often regenerated. Next, we manipulated plates vivo to place ectopically alongside columns. Ectopic induced 90-degree shift orientation nearby chondrocytes seemed inhibit...
GH is often used to treat children with idiopathic short stature despite the lack of definitive, long-term studies efficacy. We performed a randomized, double-blind, placebo-controlled trial determine effect on adult height in peripubertal children. Subjects (n = 68; 53 males and 15 females), 9–16 yr old, marked, [height or predicted ≤ −2.5 sd score (SDS)] received either (0.074 mg/kg) placebo sc three times per week until they were near height. At study termination, measurements available...
Abstract An antibody preparation to purified, homogeneous TPNH-cytochrome c reductase from pig liver microsomes was shown inhibit concomitantly (NADPH-cytochrome oxidoreductase, EC 1.6.2.3) and ethylmorphine N-demethylase activities in microsomes. The also inhibited P-450 rat bovine adrenocortical microsomes, but it did not either of these mitochondria. In addition, an adrenodoxin, the non-heme iron protein isolated mitochondria, both mitochondria any microsomal preparations, including those...
Parathyroid hormone secretion is negatively regulated by a 7-transmembrane domain, G-protein coupled Ca(2+)-sensing receptor. We hypothesized that activating mutations in this receptor might cause autosomal dominant hypoparathyroidism (ADHP). Consistent with hypothesis, we identified, two families ADHP, heterozygous missense the gene cosegregated disorder. None of 50 normal controls had either mutation. also identified de novo, mutation child severe sporadic hypoparathyroidism. The amino...
Many children with idiopathic short stature have a delayed bone age. Idiopathic advanced age is far less common.The aim was to identify underlying genetic causes of age.We used whole-exome sequencing study three families autosomal-dominant stature, age, and premature growth cessation.Affected individuals presented [adult heights -2.3 -4.2 standard deviation scores (SDS)] histories early cessation or childhood (height SDS -1.9 -3.5 SDS), advancement normal endocrine evaluations. Whole-exome...
Abstract Context: Heterozygous mutations in the aggrecan gene (ACAN) cause autosomal dominant short stature with accelerated skeletal maturation. Objective: We sought to characterize phenotypic spectrum and response growth-promoting therapies. Patients Methods: One hundred three individuals (57 females, 46 males) from 20 families heterozygous ACAN were identified confirmed using whole-exome sequencing, targeted next-generation and/or Sanger sequencing. Clinical information was collected...
Histone methyltransferases EZH1 and EZH2 catalyse the trimethylation of histone H3 at lysine 27 (H3K27), which serves as an epigenetic signal for chromatin condensation transcriptional repression. Genome-wide associated studies have implicated in control height mutations cause Weaver syndrome, includes skeletal overgrowth. Here we show that combined loss Ezh1 Ezh2 chondrocytes severely impairs growth mice. Both principal processes underlying plate chondrogenesis, chondrocyte proliferation...
Bone morphogenetic proteins (BMPs) regulate embryonic skeletal development. We hypothesized that BMP-2, which is expressed in the growth plate, also regulates plate chondrogenesis and longitudinal bone growth. To test this hypothesis, fetal rat metatarsal bones were cultured for 3 days presence of recombinant human BMP-2. The addition BMP-2 caused a concentration-dependent acceleration As rate depends primarily on chondrogenesis, we studied each its three major components. stimulated...
In humans and other mammals, the release from growth-inhibiting conditions, such as glucocorticoid excess, leads to supranormal linear growth. The prevailing explanation for this catch-up growth involves a central nervous system mechanism that compares actual body size an age-appropriate set-point adjusts rate accordingly via circulating factor. Although neuroendocrine "sizostat" was hypothesized more than 30 yr ago, its existence has never been confirmed experimentally. Here we show...
In mammals, somatic growth is rapid in early postnatal life but decelerates with age and eventually halts, thus determining the adult body size of species. This deceleration, which reflects declining proliferation, occurs simultaneously multiple organs yet appears not to be coordinated by a systemic mechanism. We, therefore, hypothesized that deceleration results from growth-limiting genetic program common tissues. Here, we identified set 11 imprinted genes show down-regulation mRNA...
Adrenal hypoplasia congenita is a rare X-linked disorder characterized by primary adrenal insufficiency and hypogonadotropic hypogonadism.1 All patients described to date have been male, female...
Sheep antibodies raised against three isoenzymes of glutathione S-transferase (EC 2.5.1.18), transferases B, C, and E, which were isolated purified to apparent homogeneity from rat liver, have been employed localize these enzymes at the light microscopic level within livers untreated rats. Using in an unlabeled antibody peroxidase-antiperoxidase staining technique, each was detected immunohistochemically parenchymal cells throughout liver lobule. In addition, immunohistochemical for C but...
In the growth plate, stem-like cells in resting zone differentiate into rapidly dividing chondrocytes of proliferative and then terminally non-dividing hypertrophic zone. To explore molecular switches responsible for this two-step differentiation program, we developed a microdissection method to isolate RNA from (RZ), (PZ), zones (HZ) 7-day-old male rats. Expression approximately 29,000 genes was analyzed by microarray selected verified real-time PCR. The analysis identified whose expression...