Calcitriol
The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (CALCIFEDIOL). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption.
24,25-Dihydroxyvitamin D 3
A physiologically active metabolite of VITAMIN D. The compound is involved in the regulation of calcium metabolism, alkaline phosphatase activity, and enhances the calcemic effect of CALCITRIOL.
Receptors, Calcitriol
Proteins, usually found in the cytoplasm, that specifically bind calcitriol, migrate to the nucleus, and regulate transcription of specific segments of DNA with the participation of D receptor interacting proteins (called DRIP). Vitamin D is converted in the liver and kidney to calcitriol and ultimately acts through these receptors.
Hydroxycholecalciferols
Hydroxy analogs of vitamin D 3; (CHOLECALCIFEROL); including CALCIFEDIOL; CALCITRIOL; and 24,25-DIHYDROXYVITAMIN D 3.
Calcifediol
The major circulating metabolite of VITAMIN D3. It is produced in the LIVER and is the best indicator of the body's vitamin D stores. It is effective in the treatment of RICKETS and OSTEOMALACIA, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties.
Vitamin D
A vitamin that includes both CHOLECALCIFEROLS and ERGOCALCIFEROLS, which have the common effect of preventing or curing RICKETS in animals. It can also be viewed as a hormone since it can be formed in SKIN by action of ULTRAVIOLET RAYS upon the precursors, 7-dehydrocholesterol and ERGOSTEROL, and acts on VITAMIN D RECEPTORS to regulate CALCIUM in opposition to PARATHYROID HORMONE.
Cholecalciferol
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
A mitochondrial cytochrome P450 enzyme that catalyzes the 1-alpha-hydroxylation of 25-hydroxyvitamin D3 (also known as 25-hydroxycholecalciferol) in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP27B1 gene, converts 25-hydroxyvitamin D3 to 1-alpha,25-dihydroxyvitamin D3 which is the active form of VITAMIN D in regulating bone growth and calcium metabolism. This enzyme is also active on plant 25-hydroxyvitamin D2 (ergocalciferol).
Steroid Hydroxylases
Ergocalciferols
Derivatives of ERGOSTEROL formed by ULTRAVIOLET RAYS breaking of the C9-C10 bond. They differ from CHOLECALCIFEROL in having a double bond between C22 and C23 and a methyl group at C24.
Receptors, Steroid
Proteins found usually in the cytoplasm or nucleus that specifically bind steroid hormones and trigger changes influencing the behavior of cells. The steroid receptor-steroid hormone complex regulates the transcription of specific genes.
Vitamin D Response Element
A DNA sequence that is found in the promoter region of vitamin D regulated genes. Vitamin D receptor (RECEPTOR, CALCITRIOL) binds to and regulates the activity of genes containing this element.
Parathyroid Hormone
A polypeptide hormone (84 amino acid residues) secreted by the PARATHYROID GLANDS which performs the essential role of maintaining intracellular CALCIUM levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of CALCIUM from BONE, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates.
Vitamin D Deficiency
A nutritional condition produced by a deficiency of VITAMIN D in the diet, insufficient production of vitamin D in the skin, inadequate absorption of vitamin D from the diet, or abnormal conversion of vitamin D to its bioactive metabolites. It is manifested clinically as RICKETS in children and OSTEOMALACIA in adults. (From Cecil Textbook of Medicine, 19th ed, p1406)
Rickets
Disorders caused by interruption of BONE MINERALIZATION manifesting as OSTEOMALACIA in adults and characteristic deformities in infancy and childhood due to disturbances in normal BONE FORMATION. The mineralization process may be interrupted by disruption of VITAMIN D; PHOSPHORUS; or CALCIUM homeostasis, resulting from dietary deficiencies, or acquired, or inherited metabolic, or hormonal disturbances.
Vitamin D-Binding Protein
An alpha-globulin found in the plasma of man and other vertebrates. It is apparently synthesized in the liver and carries vitamin D and its metabolites through the circulation and mediates the response of tissue. It is also known as group-specific component (Gc). Gc subtypes are used to determine specific phenotypes and gene frequencies. These data are employed in the classification of population groups, paternity investigations, and in forensic medicine.
Hypophosphatemia, Familial
An inherited condition of abnormally low serum levels of PHOSPHATES (below 1 mg/liter) which can occur in a number of genetic diseases with defective reabsorption of inorganic phosphorus by the PROXIMAL RENAL TUBULES. This leads to phosphaturia, HYPOPHOSPHATEMIA, and disturbances of cellular and organ functions such as those in X-LINKED HYPOPHOSPHATEMIC RICKETS; OSTEOMALACIA; and FANCONI SYNDROME.
Calcium
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
S100 Calcium Binding Protein G
A calbindin protein found in many mammalian tissues, including the UTERUS, PLACENTA, BONE, PITUITARY GLAND, and KIDNEYS. In intestinal ENTEROCYTES it mediates intracellular calcium transport from apical to basolateral membranes via calcium binding at two EF-HAND MOTIFS. Expression is regulated in some tissues by VITAMIN D.
Phosphorus
HL-60 Cells
A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)
Calbindins
Calcium-binding proteins that are found in DISTAL KIDNEY TUBULES, INTESTINES, BRAIN, and other tissues where they bind, buffer and transport cytoplasmic calcium. Calbindins possess a variable number of EF-HAND MOTIFS which contain calcium-binding sites. Some isoforms are regulated by VITAMIN D.
Calcium Channel Agonists
Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture.
Osteocalcin
Vitamin K-dependent calcium-binding protein synthesized by OSTEOBLASTS and found primarily in BONES. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. The protein contains three residues of the amino acid gamma-carboxyglutamic acid (Gla), which, in the presence of CALCIUM, promotes binding to HYDROXYAPATITE and subsequent accumulation in BONE MATRIX.
Bone and Bones
A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principle cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX.
Hypercalcemia
Abnormally high level of calcium in the blood.
Osteomalacia
Disorder caused by an interruption of the mineralization of organic bone matrix leading to bone softening, bone pain, and weakness. It is the adult form of rickets resulting from disruption of VITAMIN D; PHOSPHORUS; or CALCIUM homeostasis.
25-Hydroxyvitamin D 2
9,10-Secoergosta-5,7,10(19),22-tetraene-3,25-diol. Biologically active metabolite of vitamin D2 which is more active in curing rickets than its parent. The compound is believed to attach to the same receptor as vitamin D2 and 25-hydroxyvitamin D3.
Cell Differentiation
Vitamins
Retinoid X Receptors
A subtype of RETINOIC ACID RECEPTORS that are specific for 9-cis-retinoic acid which function as nuclear TRANSCRIPTION FACTORS that regulate multiple signaling pathways.
RNA, Messenger
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Cholestanetriol 26-Monooxygenase
Chickens
Duodenum
Osteoblasts
Intestines
Secosteroids
Osteosarcoma
Kidney
Hypophosphatemia
A condition of an abnormally low level of PHOSPHATES in the blood.
Cells, Cultured
Calcium, Dietary
Calcium compounds used as food supplements or in food to supply the body with calcium. Dietary calcium is needed during growth for bone development and for maintenance of skeletal integrity later in life to prevent osteoporosis.
Monocytes
Tumor Cells, Cultured
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Parathyroid Glands
Two pairs of small oval-shaped glands located in the front and the base of the NECK and adjacent to the two lobes of THYROID GLAND. They secrete PARATHYROID HORMONE that regulates the balance of CALCIUM; PHOSPHORUS; and MAGNESIUM in the body.
Cell Division
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Calbindin 1
A calcium-binding protein that mediates calcium HOMEOSTASIS in KIDNEYS, BRAIN, and other tissues. It is found in well-defined populations of NEURONS and is involved in CALCIUM SIGNALING and NEURONAL PLASTICITY. It is regulated in some tissues by VITAMIN D.
Dose-Response Relationship, Drug
Dihydrotachysterol
A VITAMIN D that can be regarded as a reduction product of vitamin D2.
Cytochrome P-450 Enzyme System
A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.
Keratinocytes
Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell.
Tretinoin
An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).
Leukemia, Promyelocytic, Acute
Gene Expression Regulation
Familial Hypophosphatemic Rickets
A hereditary disorder characterized by HYPOPHOSPHATEMIA; RICKETS; OSTEOMALACIA; renal defects in phosphate reabsorption and vitamin D metabolism; and growth retardation. Autosomal and X-linked dominant and recessive variants have been reported.
Transcription, Genetic
Alkaline Phosphatase
Receptors, Retinoic Acid
Intestinal Absorption
Uptake of substances through the lining of the INTESTINES.
Calcitonin
A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults.
Fibroblast Growth Factors
A family of small polypeptide growth factors that share several common features including a strong affinity for HEPARIN, and a central barrel-shaped core region of 140 amino acids that is highly homologous between family members. Although originally studied as proteins that stimulate the growth of fibroblasts this distinction is no longer a requirement for membership in the fibroblast growth factor family.
Hypocalcemia
Reduction of the blood calcium below normal. Manifestations include hyperactive deep tendon reflexes, Chvostek's sign, muscle and abdominal cramps, and carpopedal spasm. (Dorland, 27th ed)
Promoter Regions, Genetic
Chromatography, High Pressure Liquid
Osteoclasts
A large multinuclear cell associated with the BONE RESORPTION. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in CEMENTUM resorption.
Hypoparathyroidism
A condition caused by a deficiency of PARATHYROID HORMONE (or PTH). It is characterized by HYPOCALCEMIA and hyperphosphatemia. Hypocalcemia leads to TETANY. The acquired form is due to removal or injuries to the PARATHYROID GLANDS. The congenital form is due to mutations of genes, such as TBX1; (see DIGEORGE SYNDROME); CASR encoding CALCIUM-SENSING RECEPTOR; or PTH encoding parathyroid hormone.
Cytosol
Sodium-Phosphate Cotransporter Proteins, Type IIc
Up-Regulation
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Cycloheximide
Hypercalciuria
Excretion of abnormally high level of CALCIUM in the URINE, greater than 4 mg/kg/day.
Calcium Metabolism Disorders
Disorders in the processing of calcium in the body: its absorption, transport, storage, and utilization.
Tetradecanoylphorbol Acetate
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
Enzyme Induction
Gene Expression
Parathyroid Hormone-Related Protein
A ubiquitously expressed, secreted protein with bone resorption and renal calcium reabsorption activities that are similar to PARATHYROID HORMONE. It does not circulate in appreciable amounts in normal subjects, but rather exerts its biological actions locally. Overexpression of parathyroid hormone-related protein by tumor cells results in humoral calcemia of malignancy.
Base Sequence
Cholesterol Side-Chain Cleavage Enzyme
A mitochondrial cytochrome P450 enzyme that catalyzes the side-chain cleavage of C27 cholesterol to C21 pregnenolone in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP11A1 gene, catalyzes the breakage between C20 and C22 which is the initial and rate-limiting step in the biosynthesis of various gonadal and adrenal steroid hormones.
Teriparatide
A polypeptide that consists of the 1-34 amino-acid fragment of human PARATHYROID HORMONE, the biologically active N-terminal region. The acetate form is given by intravenous infusion in the differential diagnosis of HYPOPARATHYROIDISM and PSEUDOHYPOPARATHYROIDISM. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995)
Hydroxylation
Dactinomycin
A compound composed of a two CYCLIC PEPTIDES attached to a phenoxazine that is derived from STREPTOMYCES parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015)
PHEX Phosphate Regulating Neutral Endopeptidase
A membrane-bound metalloendopeptidase that may play a role in the degradation or activation of a variety of PEPTIDE HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Genetic mutations that result in loss of function of this protein are a cause of HYPOPHOSPHATEMIC RICKETS, X-LINKED DOMINANT.
Cell Line, Tumor
A cell line derived from cultured tumor cells.
Caco-2 Cells
Calcification, Physiologic
Process by which organic tissue becomes hardened by the physiologic deposit of calcium salts.
Blotting, Northern
Reverse Transcriptase Polymerase Chain Reaction
Hyperparathyroidism, Secondary
Abnormally elevated PARATHYROID HORMONE secretion as a response to HYPOCALCEMIA. It is caused by chronic KIDNEY FAILURE or other abnormalities in the controls of bone and mineral metabolism, leading to various BONE DISEASES, such as RENAL OSTEODYSTROPHY.
TRPV Cation Channels
A subgroup of TRP cation channels named after vanilloid receptor. They are very sensitive to TEMPERATURE and hot spicy food and CAPSAICIN. They have the TRP domain and ANKYRIN repeats. Selectivity for CALCIUM over SODIUM ranges from 3 to 100 fold.
Binding, Competitive
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
Calcium-Binding Proteins
Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.
Intestinal Mucosa
Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.
Transcription Factors
Ligands
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
Glucuronidase
U937 Cells
A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation.
Structure-Activity Relationship
Response Elements
Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promoter and enhancer regions.
Osteopontin
A negatively-charged extracellular matrix protein that plays a role in the regulation of BONE metabolism and a variety of other biological functions. Cell signaling by osteopontin may occur through a cell adhesion sequence that recognizes INTEGRIN ALPHA-V BETA-3.
Transfection
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Lithocholic Acid
A bile acid formed from chenodeoxycholate by bacterial action, usually conjugated with glycine or taurine. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as cholagogue and choleretic.
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Cell Proliferation
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Sialoglycoproteins
Leukemia, Myeloid, Acute
Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.
Bone Development
The growth and development of bones from fetus to adult. It includes two principal mechanisms of bone growth: growth in length of long bones at the epiphyseal cartilages and growth in thickness by depositing new bone (OSTEOGENESIS) with the actions of OSTEOBLASTS and OSTEOCLASTS.
Macrophages
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
RANK Ligand
A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B and OSTEOPROTEGERIN. It plays an important role in regulating OSTEOCLAST differentiation and activation.
Nephrectomy
Excision of kidney.
Sarcoidosis
An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands.
Rats, Inbred Strains
Blotting, Western
Intestine, Small
The portion of the GASTROINTESTINAL TRACT between the PYLORUS of the STOMACH and the ILEOCECAL VALVE of the LARGE INTESTINE. It is divisible into three portions: the DUODENUM, the JEJUNUM, and the ILEUM.
Sodium-Phosphate Cotransporter Proteins, Type IIa
Gene Expression Regulation, Enzymologic
Signal Transduction
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Mice, Knockout
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Skin
The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
Leukemia, Myeloid
Phosphorus, Dietary
Phosphorus used in foods or obtained from food. This element is a major intracellular component which plays an important role in many biochemical pathways relating to normal physiological functions. High concentrations of dietary phosphorus can cause nephrocalcinosis which is associated with impaired kidney function. Low concentrations of dietary phosphorus cause an increase in calcitriol in the blood and osteoporosis.
Hormones
Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various ENDOCRINE GLANDS and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects.
Dimethyl Sulfoxide
A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during CRYOPRESERVATION. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation.
Homeostasis
Mediator Complex Subunit 1
A mediator complex subunit that is believed to play a key role in the coactivation of nuclear receptor-activated transcription by the mediator complex. It interacts with a variety of nuclear receptors including RETINOIC ACID RECEPTORS; THYROID HORMONE RECEPTORS; VITAMIN D RECEPTORS; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; ESTROGEN RECEPTORS; and GLUCOCORTICOID RECEPTORS.
Cell Nucleus
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Binding Sites
Parturient Paresis
A disease of pregnant and lactating cows and ewes leading to generalized paresis and death. The disease, which is characterized by hypocalcemia, occurs at or shortly after parturition in cows and within weeks before or after parturition in ewes.
DNA
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Growth Inhibitors
Cyclin C
A cyclin subtype that binds to the CYCLIN-DEPENDENT KINASE 3 and CYCLIN-DEPENDENT KINASE 8. Cyclin C plays a dual role as a transcriptional regulator and a G1 phase CELL CYCLE regulator.
Down-Regulation
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Mass Spectrometry
Protein Binding
Minerals
Native, inorganic or fossilized organic substances having a definite chemical composition and formed by inorganic reactions. They may occur as individual crystals or may be disseminated in some other mineral or rock. (Grant & Hackh's Chemical Dictionary, 5th ed; McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Santonin
Pseudohypoparathyroidism
A hereditary syndrome clinically similar to HYPOPARATHYROIDISM. It is characterized by HYPOCALCEMIA; HYPERPHOSPHATEMIA; and associated skeletal development impairment and caused by failure of response to PARATHYROID HORMONE rather than deficiencies. A severe form with resistance to multiple hormones is referred to as Type 1a and is associated with maternal mutant allele of the ALPHA CHAIN OF STIMULATORY G PROTEIN.
Phosphorus Metabolism Disorders
Disorders in the processing of phosphorus in the body: its absorption, transport, storage, and utilization.
Osteoprotegerin
A secreted member of the TNF receptor superfamily that negatively regulates osteoclastogenesis. It is a soluble decoy receptor of RANK LIGAND that inhibits both CELL DIFFERENTIATION and function of OSTEOCLASTS by inhibiting the interaction between RANK LIGAND and RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B.
COS Cells
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
Transcriptional Activation
Dehydrocholesterols
Mesenchymoma
Apolipoproteins D
A glycoprotein component of HIGH-DENSITY LIPOPROTEINS that transports small hydrophobic ligands including CHOLESTEROL and STEROLS. It occurs in the macromolecular complex with LECITHIN CHOLESTEROL ACYLTRANSFERASE. Apo D is expressed in and secreted from a variety of tissues such as liver, placenta, brain tissue and others.
Gene Expression Regulation, Neoplastic
Antigens, CD14
Glycolipid-anchored membrane glycoproteins expressed on cells of the myelomonocyte lineage including monocytes, macrophages, and some granulocytes. They function as receptors for the complex of lipopolysaccharide (LPS) and LPS-binding protein.
Receptor Activator of Nuclear Factor-kappa B
A tumor necrosis factor receptor family member that is specific for RANK LIGAND and plays a role in bone homeostasis by regulating osteoclastogenesis. It is also expressed on DENDRITIC CELLS where it plays a role in regulating dendritic cell survival. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Rats, Sprague-Dawley
Hyperparathyroidism
A condition of abnormally elevated output of PARATHYROID HORMONE (or PTH) triggering responses that increase blood CALCIUM. It is characterized by HYPERCALCEMIA and BONE RESORPTION, eventually leading to bone diseases. PRIMARY HYPERPARATHYROIDISM is caused by parathyroid HYPERPLASIA or PARATHYROID NEOPLASMS. SECONDARY HYPERPARATHYROIDISM is increased PTH secretion in response to HYPOCALCEMIA, usually caused by chronic KIDNEY DISEASES.
Betamethasone Valerate
Receptors, Calcium-Sensing
A class of G-protein-coupled receptors that react to varying extracellular CALCIUM levels. Calcium-sensing receptors in the PARATHYROID GLANDS play an important role in the maintenance of calcium HOMEOSTASIS by regulating the release of PARATHYROID HORMONE. They differ from INTRACELLULAR CALCIUM-SENSING PROTEINS which sense intracellular calcium levels.
DNA Primers
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Bone Density
The amount of mineral per square centimeter of BONE. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by X-RAY ABSORPTIOMETRY or TOMOGRAPHY, X RAY COMPUTED. Bone density is an important predictor for OSTEOPOROSIS.
Mice, Inbred C57BL
Inbred C57BL mice are a strain of laboratory mice that have been produced by many generations of brother-sister matings, resulting in a high degree of genetic uniformity and homozygosity, making them widely used for biomedical research, including studies on genetics, immunology, cancer, and neuroscience.
Bone Marrow Cells
Endothelin-3
A 21-amino acid peptide that circulates in the plasma, but its source is not known. Endothelin-3 has been found in high concentrations in the brain and may regulate important functions in neurons and astrocytes, such as proliferation and development. It also is found throughout the gastrointestinal tract and in the lung and kidney. (N Eng J Med 1995;333(6):356-63)
Apoptosis
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Cell Cycle
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
Carrier Proteins
Epidermis
The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of EPITHELIUM: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis).
Granulocytes
Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the NEUTROPHILS; EOSINOPHILS; and BASOPHILS.
Absorption
Arylsulfatases
Enzymes that catalyze the hydrolysis of a phenol sulfate to yield a phenol and sulfate. Arylsulfatase A, B, and C have been separated. A deficiency of arylsulfatases is one of the causes of metachromatic leukodystrophy (LEUKODYSTROPHY, METACHROMATIC). EC 3.1.6.1.
Paraneoplastic Syndromes
Gene Expression Regulation, Leukemic
Cell Line, Transformed
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
Recombinant Proteins
Proteins prepared by recombinant DNA technology.
DNA-Binding Proteins
Vitamin K
A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: VITAMIN K 1 (phytomenadione) derived from plants, VITAMIN K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, VITAMIN K 3 (menadione). Vitamin K 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin K. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin K.
Leukemia, Monocytic, Acute
An acute myeloid leukemia in which 80% or more of the leukemic cells are of monocytic lineage including monoblasts, promonocytes, and MONOCYTES.
Acid Phosphatase
Tritium
Tritium is an isotope of hydrogen (specifically, hydrogen-3) that contains one proton and two neutrons in its nucleus, making it radioactive with a half-life of about 12.3 years, and is used in various applications including nuclear research, illumination, and dating techniques due to its low energy beta decay.
Bone Density Conservation Agents
Agents that inhibit BONE RESORPTION and/or favor BONE MINERALIZATION and BONE REGENERATION. They are used to heal BONE FRACTURES and to treat METABOLIC BONE DISEASES such as OSTEOPOROSIS.
Trimethylsilyl Compounds
Fat Substitutes
Compounds used in food or in food preparation to replace dietary fats. They may be carbohydrate-, protein-, or fat-based. Fat substitutes are usually lower in calories but provide the same texture as fats.
Stereoisomerism
Interferon-gamma
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
Isoenzymes
Biological Assay
A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. It includes virulence studies in animal fetuses in utero, mouse convulsion bioassay of insulin, quantitation of tumor-initiator systems in mouse skin, calculation of potentiating effects of a hormonal factor in an isolated strip of contracting stomach muscle, etc.
Protein Kinase C
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
Biological Markers
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
Calcium Channels
Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.
Chloramphenicol O-Acetyltransferase
An enzyme that catalyzes the acetylation of chloramphenicol to yield chloramphenicol 3-acetate. Since chloramphenicol 3-acetate does not bind to bacterial ribosomes and is not an inhibitor of peptidyltransferase, the enzyme is responsible for the naturally occurring chloramphenicol resistance in bacteria. The enzyme, for which variants are known, is found in both gram-negative and gram-positive bacteria. EC 2.3.1.28.
Genes, Reporter
Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.
Receptors, Cytoplasmic and Nuclear
Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.