Cortodoxone: 17,21-Dihydroxypregn-4-ene-3,20-dione. A 17-hydroxycorticosteroid with glucocorticoid and anti-inflammatory activities.Mucorales: An order of zygomycetous fungi, usually saprophytic, causing damage to food in storage, but which may cause respiratory infection or MUCORMYCOSIS in persons suffering from other debilitating diseases.17-Hydroxycorticosteroids: A group of hydroxycorticosteroids bearing a hydroxy group at the 17-position. Urinary excretion of these compounds is used as an index of adrenal function. They are used systemically in the free alcohol form, but with esterification of the hydroxy groups, topical effectiveness is increased.Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)17-alpha-Hydroxyprogesterone: A metabolite of PROGESTERONE with a hydroxyl group at the 17-alpha position. It serves as an intermediate in the biosynthesis of HYDROCORTISONE and GONADAL STEROID HORMONES.Hydrocortisone: The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.Metyrapone: An inhibitor of the enzyme STEROID 11-BETA-MONOOXYGENASE. It is used as a test of the feedback hypothalamic-pituitary mechanism in the diagnosis of CUSHING SYNDROME.Organophosphonates: Carbon-containing phosphonic acid compounds. Included under this heading are compounds that have carbon bound to either OXYGEN atom or the PHOSPHOROUS atom of the (P=O)O2 structure.Patents as Topic: Exclusive legal rights or privileges applied to inventions, plants, etc.Amination: The creation of an amine. It can be produced by the addition of an amino group to an organic compound or reduction of a nitro group.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.Phosphorus: A non-metal element that has the atomic symbol P, atomic number 15, and atomic weight 31. It is an essential element that takes part in a broad variety of biochemical reactions.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Stereoisomerism: The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Wound Healing: Restoration of integrity to traumatized tissue.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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Inventions: A novel composition, device, or process, independently conceived de novo or derived from a pre-existing model.Skin: The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.Intellectual Property: Property, such as patents, trademarks, and copyright, that results from creative effort. The Patent and Copyright Clause (Art. 1, Sec. 8, cl. 8) of the United States Constitution provides for promoting the progress of science and useful arts by securing for limited times to authors and inventors, the exclusive right to their respective writings and discoveries. (From Black's Law Dictionary, 5th ed, p1014)Emulsions: Colloids formed by the combination of two immiscible liquids such as oil and water. Lipid-in-water emulsions are usually liquid, like milk or lotion. Water-in-lipid emulsions tend to be creams. The formation of emulsions may be aided by amphiphatic molecules that surround one component of the system to form MICELLES.Polysorbates: Sorbitan mono-9-octadecanoate poly(oxy-1,2-ethanediyl) derivatives; complex mixtures of polyoxyethylene ethers used as emulsifiers or dispersing agents in pharmaceuticals.SqualeneOils: Unctuous combustible substances that are liquid or easily liquefiable on warming, and are soluble in ether but insoluble in water. Such substances, depending on their origin, are classified as animal, mineral, or vegetable oils. Depending on their behavior on heating, they are volatile or fixed. (Dorland, 28th ed)Fatty Alcohols: Usually high-molecular-weight, straight-chain primary alcohols, but can also range from as few as 4 carbons, derived from natural fats and oils, including lauryl, stearyl, oleyl, and linoleyl alcohols. They are used in pharmaceuticals, cosmetics, detergents, plastics, and lube oils and in textile manufacture. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Emollients: Oleagenous substances used topically to soothe, soften or protect skin or mucous membranes. They are used also as vehicles for other dermatologic agents.Waxes: A plastic substance deposited by insects or obtained from plants. Waxes are esters of various fatty acids with higher, usually monohydric alcohols. The wax of pharmacy is principally yellow wax (beeswax), the material of which honeycomb is made. It consists chiefly of cerotic acid and myricin and is used in making ointments, cerates, etc. (Dorland, 27th ed)Short-Wave Therapy: The use of focused short radio waves to produce local hyperthermia in an injured person or diseased body area.Periosteum: Thin outer membrane that surrounds a bone. It contains CONNECTIVE TISSUE, CAPILLARIES, nerves, and a number of cell types.Equipment and Supplies: Expendable and nonexpendable equipment, supplies, apparatus, and instruments that are used in diagnostic, surgical, therapeutic, scientific, and experimental procedures.Device Approval: Process that is gone through in order for a device to receive approval by a government regulatory agency. This includes any required preclinical or clinical testing, review, submission, and evaluation of the applications and test results, and post-marketing surveillance. It is not restricted to FDA.Equipment Safety: Freedom of equipment from actual or potential hazards.Medical Device Legislation: Laws and regulations pertaining to devices used in medicine, proposed for enactment, or enacted by a legislative body.United States Food and Drug Administration: An agency of the PUBLIC HEALTH SERVICE concerned with the overall planning, promoting, and administering of programs pertaining to maintaining standards of quality of foods, drugs, therapeutic devices, etc.Endometrium: The mucous membrane lining of the uterine cavity that is hormonally responsive during the MENSTRUAL CYCLE and PREGNANCY. The endometrium undergoes cyclic changes that characterize MENSTRUATION. After successful FERTILIZATION, it serves to sustain the developing embryo.Stem Cells: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.Game Theory: Theoretical construct used in applied mathematics to analyze certain situations in which there is an interplay between parties that may have similar, opposed, or mixed interests. In a typical game, decision-making "players," who each have their own goals, try to gain advantage over the other parties by anticipating each other's decisions; the game is finally resolved as a consequence of the players' decisions.Games, Experimental: Games designed to provide information on hypotheses, policies, procedures, or strategies.Punishment: The application of an unpleasant stimulus or penalty for the purpose of eliminating or correcting undesirable behavior.Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive.Adrenal Insufficiency: Conditions in which the production of adrenal CORTICOSTEROIDS falls below the requirement of the body. Adrenal insufficiency can be caused by defects in the ADRENAL GLANDS, the PITUITARY GLAND, or the HYPOTHALAMUS.Thyroid (USP): A dehydrated extract of thyroid glands from domesticated animals. After the removal of fat and connective tissue, the extract is dried or lyophilized to yield a yellowish to buff-colored amorphous powder containing 0.17-0.23% of iodine.Xerostomia: Decreased salivary flow.Adrenal Glands: A pair of glands located at the cranial pole of each of the two KIDNEYS. Each adrenal gland is composed of two distinct endocrine tissues with separate embryonic origins, the ADRENAL CORTEX producing STEROIDS and the ADRENAL MEDULLA producing NEUROTRANSMITTERS.Submandibular Gland: One of two salivary glands in the neck, located in the space bound by the two bellies of the digastric muscle and the angle of the mandible. It discharges through the submandibular duct. The secretory units are predominantly serous although a few mucous alveoli, some with serous demilunes, occur. (Stedman, 25th ed)Adrenal Gland Diseases: Pathological processes of the ADRENAL GLANDS.Addison Disease: An adrenal disease characterized by the progressive destruction of the ADRENAL CORTEX, resulting in insufficient production of ALDOSTERONE and HYDROCORTISONE. Clinical symptoms include ANOREXIA; NAUSEA; WEIGHT LOSS; MUSCLE WEAKNESS; and HYPERPIGMENTATION of the SKIN due to increase in circulating levels of ACTH precursor hormone which stimulates MELANOCYTES.Fludrocortisone: A synthetic mineralocorticoid with anti-inflammatory activity.Mineralocorticoids: A group of CORTICOSTEROIDS primarily associated with water and electrolyte balance. This is accomplished through the effect on ION TRANSPORT in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by PLASMA VOLUME, serum potassium, and ANGIOTENSIN II.Adrenal Cortex HormonesPrednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states.

A radioimmunoassay for human plasma corticosterone. (1/79)

A radioimmunoassay for human plasma corticosterone has been developed. Antiserum against corticosterone was produced in rabbits immunized with corticosterone-21-hemisuccinate conjugated to bovine serum albumin. The antiserum cross-reacted with progesterone, DOC and dehydrocorticosterone more than 20%. After the extraction with ether, and the separation by Sephadex LH-20 microcolumn chromatography, recovery was 51.2 +/- 12.1% in 50 assays. The mean coefficient of variation between assays was 7.7% and within assays was 8.6%. Human plasma corticosterone is measured readily by assaying aliquots of an ether extract of 0.05 to 0.1 ml of plasma after microcolumn chromatography. The mean plasma corticosterone concentration at 9 a.m. was 7.1 +/- 3.2 ng/ml in 45 normal subjects. Plasma corticosterone increased 5.2 times as much as basal values after ACTH injection, whereas radioimmunoassayed cortisol increased 2.4 times. On the other hand, plasma corticosterone decreased to 22.6% of basal values at four hours after 1 mg dexamethasone, whereas radioimmunoassayed cortisol decreased to 12.3% of basal values.  (+info)

Radioimmunoassay for 11-deoxycortisol using iodine-labeled tracer. (2/79)

A simple and sensitive radioimmunoassay for 11-deoxycortisol was developed. The antiserum produced in rabbits by immunizing with a complex of 11-deoxycortisol-3-oxime and bovine serum albumin (BSA) has little cross-reactivity with other endogenous steroids. The immunoassay procedure requires only one-step ethanol denaturation of binding proteins in plasma and extraction by an organic solvent can be omitted. Furthermore, use of 125I-labeled tracer significantly simplify the counting procedure. The method is sensitive enough to detect 1 microng/100 ml of 11-deoxycortisol. Plasma 11-deoxycortisol levels measured by this method after the administration of a single dose of metyrapone ranged from 5.0 to 19.2 microng/100 ml, whereas they were 0 to 4.0 microng/100 ml in hypopituitary patients. It is concluded that this simple method is useful for the routine assay of plasma 11-deoxycortisol as a parameter of the metyrapone tests.  (+info)

Changes in the specificity of antibodies by site-specific mutagenesis followed by random mutagenesis. (3/79)

The specificity for 11-deoxycortisol (11-DOC) of a monoclonal antibody (mAb), designated SCET, was changed to specificity for cortisol (CS) by site-specific mutagenesis followed by random mutagenesis. The Fab form of SCET was expressed on the surface of a phage. During the first step, mutations were introduced at 14 amino acid positions in three complementarity-determining regions (CDRs) of the VH domain that seemed likely to form the steroid-binding pocket. A clone, DcC16, was isolated from the resultant library with multiple mutations and this clone was shown to have CS-binding activity but also to retain high 11-DOC-binding activity. During the second step, mutations were introduced randomly into the entire VH-coding region of the DcC16 clone by an error-prone polymerase chain reaction, and CS-specific mutant antibodies were selected in the presence of 11-DOC as a competitor. Three representative clones were analyzed with the BIAcore instrument, and each revealed a large increase in the binding constant for CS and a decrease in that for 11-DOC. Structural models, constructed by computer simulation, indicated the probable molecular basis for these changes in specificity.  (+info)

Apparent activities of 21-hydroxylase, 17alpha-hydroxylase and 17,20-lyase are impaired in adrenal incidentalomas. (4/79)

OBJECTIVE: An increased response of 17-hydroxyprogesterone to ACTH stimulation has been observed in adrenal incidentaloma and linked to an impairment of either 21-hydroxylase or of 11beta-hydroxylase activity. To analyse this question further, we investigated the steroidogenic pathways in a series of 17 adrenal incidentalomas. DESIGN AND PATIENTS: 17 patients (7 women, 10 men; mean age, 62 +/- 12 years) with non-histologically analyzed adrenal incidentalomas were prospectively evaluated. METHODS: The following variables were investigated: 24-h urinary methanephrines and free cortisol excretion; plasma levels of ACTH and dehydroepiandrosterone; overnight dexamethasone suppression test; 1-24 ACTH stimulation test with measurement of: cortisol, 11-deoxycortisol, 17-hydroxyprogesterone, aldosterone, 11-deoxycorticosterone, progesterone, 17-hydroxypregnenolone, Delta4-androstenedione, dehydroepiandrosterone and 21-deoxycortisol. RESULTS: Discordant features of subclinical hypercorticism were noted in one case. No patient had dehydroepiandrosterone sulfate levels in the normal range for his or her age. Peak 17-hydroxyprogesterone and peak 21-deoxycortisol disclosed impairment of 21-hydroxylase in 11 and 10 cases respectively. An increased 11-deoxycortisol/cortisol ratio identified reduced activity of 11beta-hydroxylase in 11 patients. Eight patients displayed features of mild 17,20-lyase impairment, which was related to 21-hydroxylase dysfunction. Whereas only 2 patients showed no enzyme modification, 9 displayed alterations of at least two pathways. CONCLUSION: In our hands, a combination of enzyme dysfunction was frequently observed. Shared biochemical mechanisms could explain combined 17,20-lyase and 21-hydroxylase alterations, whereas coexistence of 21-hydroxylase (particularly when based on peak 21-deoxycortisol) and 11beta-hydroxylase is more puzzling.  (+info)

Effects of insulin-like growth factor-I on in vitro final oocyte maturation and ovarian steroidogenesis in striped bass, Morone saxatilis. (5/79)

Recombinant human (rh) insulin-like growth factor-I (IGF-I) was more potent than rhIGF-II at inducing in vitro germinal vesicle breakdown (GVBD), a marker for resumption of meiosis, in oocytes of striped bass. Treatment of ovarian fragments containing oocytes in intact follicles with rhIGF-I increased concentrations of estradiol-17beta and maturation-inducing steroid (MIS) 17,20beta, 21-trihydoxy-4-pregnen-3-one (20beta-S) in the culture medium and decreased testosterone levels. The follicles were too immature for oocytes to complete GVBD in response to 20beta-S (MIS incompetent) or hCG. Addition of 20beta-S to cultures did not increase the percentage of oocytes completing GVBD in response to rhIGF-I or rhIGF-II. Bovine insulin was without effect on GVBD or steroid production. Incubation of MIS-competent follicles with actinomycin D, cyanoketone, trilostane, 1-heptanol, or 1-octanol had no effect on rhIGF-I-induced GVBD, but attenuated hCG-induced GVBD and 20beta-S production. Cycloheximide inhibited rhIGF-I-induced GVBD. Collectively, these observations indicate that IGF-I can induce GVBD via MIS- and transcription-independent pathways without coupled gap junctions between oocytes and granulosa cells or among granulosa cells, but requires protein synthesis to do so. An rhIGF-I analogue that does not bind IGF-binding proteins, des(1,3)IGF-I, was more potent than rhIGF-I in inducing GVBD, suggesting ovarian IGF-binding proteins may inhibit IGF-I action.  (+info)

Nonchromatographic radioimmunoassay of plasma 11-deoxycortisol, for use in the metyrapone test, with polyethylene glycol as the precipant. (6/79)

We have developed a simple, reliable radioimmunoassay for plasma 11-deoxycortisol. The method does not require chromatography but instead makes use of a simple extraction procedure which, in combination with the antibody characteristics, is highly specific for the metyrapone test. Polyethylene glycol was used to separate free and antibody-bound steroid. The smallest amount measurable is 15 pg (2.0 mug/liter of plasma). The method is shown to be precise and accurate. Intraassay precision of the method for two plasma pools was 26.7 plus or minus 2.5 mug/liter (CV equals 9.4%) and 61.2 plus or minus 3.7 mug/liter (CV equals 6.0%). The respective inter-assay precision was 27.0 plus or minus 1.7 mug/liter (CV equals 6.3%) and 59.9 plus or minus 2.3 mug/liter (CV equals 3.8%). The validity of the assay was further verified by evaluating the plasma 11-deoxycortisol response to metyrapone administration. The relative simplicity of the method and the commercial availability of all reagents, including antisera, makes this radioimmunoassay procedure practical for use in clinical laboratories.  (+info)

CYP11A1 stimulates the hydroxylase activity of CYP11B1 in mitochondria of recombinant yeast in vivo and in vitro. (7/79)

In mammals, hydrocortisone synthesis from cholesterol is catalyzed by a set of five specialized enzymes, four of them belonging to the superfamily of cytochrome P-450 monooxygenases. A recombinant yeast expression system was recently developed for the CYP11B1 (P45011beta) enzyme, which performs the 11beta hydroxylation of steroids such as 11-deoxycortisol into hydrocortisone, one of the three mitochondrial cytochrome P-450 proteins involved in steroidogenesis in mammals. This heterologous system was used to test the potential interaction between CYP11B1 and CYP11A1 (P450scc), the mitochondrial cytochrome P-450 enzyme responsible for the side chain cleaving of cholesterol. Recombinant CYP11B1 and CYP11A1 were targeted to Saccharomyces cerevisiae mitochondria using the yeast cytochrome oxidase subunit 6 mitochondrial presequence fused to the mature form of the two proteins. In yeast, the presence of CYP11A1 appears to improve 11beta hydroxylase activity of CYP11B1 in vivo and in vitro. Fractionation experiments indicate the presence of the two proteins in the same membrane fractions, i.e. inner membrane and contact sites of mitochondria. Thus, yeast mitochondria provide interesting insights to study some molecular and cellular aspects of mammalian steroid synthesis. In particular, recombinant yeast should permit a better understanding of the mechanism permitting the synthesis of steroids (sex steroids, mineralocorticoids and glucocorticoids) with a minimal set of enzymes at physiological level, thus avoiding disease states.  (+info)

Parallel radioimmunoassay for plasma cortisol and 11-deoxycortisol. (8/79)

We describe a direct, rapid, and specific procedure for the parallel radioimmunoassay for cortisol and 11-deoxycortisol in plasma. The plasma sample is used directly, after heat inactivation of the natural cortisol-binding protein. The radioimmunoassay utilizes antibodies generated in rabbits by steroids congugated at their 3-oxo position to thyroglobulin. Ammonium sulfate is used to separate bound and free steroids. Our cortisol antibody and an 11-deoxycortisol antibody obtained elsewhere cross reacted negligibly with each other or with other steroids that might be present in plasma. Radioimmunoassays were therefore developed for both steroids in only 1.25 mul of plasma. The intra- and inter-assay coefficients of variation for both steroids were less than 10%, with a sensitivyt of 4 mug/liter. Steroid values obtained by a competitive protein binding method were consistently higher than those of the present method, suggesting that the former is measuring total corticosteroids. This simple approach requires only 4 h for the specific measurement of both cortisol and 11-deoxycortisol in 20 samples of plasma.  (+info)

  • 11-Deoxycortisol , also known as cortodoxone ( INN ) or cortexolone , as well as 17α,21-dihydroxyprogesterone or 17α,21-dihydroxypregn-4-ene-3,20-dione , is a glucocorticoid steroid hormone . (wikipedia.org)
  • Dimethisterone, also known as 6α,21-dimethylethisterone or as 6α,21-dimethyl-17α-ethynyltestosterone, as well as 17α-ethynyl-6α,21-dimethylandrost-4-en-17β-ol-3-one or as 6α,21-dimethyl-17β-hydroxy-17α-pregn-4-en-20-yn-3-one, is a synthetic androstane steroid and a derivative of testosterone . (readtiger.com)