Biomaterial Database

Antiprogestins and iatrogenic glucocorticoid resistance. 1997

J W Koper, and G J Molijn, and C J van Uffelen, and E Stigter, and S W Lamberts

Department of Internal Medicine III, Erasmus University Rotterdam, The Netherlands. koper@inw3.fgg.eur.nl

The antiglucocorticoid action of the antiprogestin RU 38486 has interfered with its successful clinical application in long-term treatment. Several new antiprogestins (Org 31710, Org 31806 and ZK 98299) have recently been developed with the aim to eliminate this side-effect. We have used a human lymphocyte proliferation assay to estimate the antiglucocorticoid potency of RU 38486 and the newer antiprogestins. In this assay 100 nmol/L RU 38486 shifted the dexamethasone inhibition curve by at least one order of magnitude. The other antiprogestins showed no effect at 100 nmol/L. RU 38486 (30 nmol/L) was able to antagonize 1000 nmol/L dexamethasone. The other antiprogestins showed only slight effects even at 1000 nmol/L. We conclude that the new antiprogestins have antiglucocorticoid effects that are one to two orders of magnitude lower than that of RU 38486. This may make them more suitable than RU 38486 for application in long-term antiprogestin treatment.

UI	MeSH Term	Description	Entries
D008213	Lymphocyte Activation	Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.	Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D008577	Meningeal Neoplasms	Benign and malignant neoplastic processes that arise from or secondarily involve the meningeal coverings of the brain and spinal cord.	Intracranial Meningeal Neoplasms,Spinal Meningeal Neoplasms,Benign Meningeal Neoplasms,Leptomeningeal Neoplasms,Malignant Meningeal Neoplasms,Meningeal Cancer,Meningeal Neoplasms, Benign,Meningeal Neoplasms, Intracranial,Meningeal Neoplasms, Malignant,Meningeal Tumors,Neoplasms, Leptomeningeal,Neoplasms, Meningeal,Benign Meningeal Neoplasm,Cancer, Meningeal,Cancers, Meningeal,Intracranial Meningeal Neoplasm,Leptomeningeal Neoplasm,Malignant Meningeal Neoplasm,Meningeal Cancers,Meningeal Neoplasm,Meningeal Neoplasm, Benign,Meningeal Neoplasm, Intracranial,Meningeal Neoplasm, Malignant,Meningeal Neoplasm, Spinal,Meningeal Neoplasms, Spinal,Meningeal Tumor,Neoplasm, Benign Meningeal,Neoplasm, Intracranial Meningeal,Neoplasm, Leptomeningeal,Neoplasm, Malignant Meningeal,Neoplasm, Meningeal,Neoplasm, Spinal Meningeal,Neoplasms, Benign Meningeal,Neoplasms, Intracranial Meningeal,Neoplasms, Malignant Meningeal,Neoplasms, Spinal Meningeal,Spinal Meningeal Neoplasm,Tumor, Meningeal,Tumors, Meningeal
D008579	Meningioma	A relatively common neoplasm of the CENTRAL NERVOUS SYSTEM that arises from arachnoidal cells. The majority are well differentiated vascular tumors which grow slowly and have a low potential to be invasive, although malignant subtypes occur. Meningiomas have a predilection to arise from the parasagittal region, cerebral convexity, sphenoidal ridge, olfactory groove, and SPINAL CANAL. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2056-7)	Benign Meningioma,Malignant Meningioma,Meningiomas, Multiple,Meningiomatosis,Angioblastic Meningioma,Angiomatous Meningioma,Cerebral Convexity Meningioma,Clear Cell Meningioma,Fibrous Meningioma,Hemangioblastic Meningioma,Hemangiopericytic Meningioma,Intracranial Meningioma,Intraorbital Meningioma,Intraventricular Meningioma,Meningotheliomatous Meningioma,Microcystic Meningioma,Olfactory Groove Meningioma,Papillary Meningioma,Parasagittal Meningioma,Posterior Fossa Meningioma,Psammomatous Meningioma,Secretory Meningioma,Sphenoid Wing Meningioma,Spinal Meningioma,Transitional Meningioma,Xanthomatous Meningioma,Angioblastic Meningiomas,Angiomatous Meningiomas,Benign Meningiomas,Cerebral Convexity Meningiomas,Clear Cell Meningiomas,Convexity Meningioma, Cerebral,Convexity Meningiomas, Cerebral,Fibrous Meningiomas,Groove Meningiomas, Olfactory,Hemangioblastic Meningiomas,Hemangiopericytic Meningiomas,Intracranial Meningiomas,Intraorbital Meningiomas,Intraventricular Meningiomas,Malignant Meningiomas,Meningioma, Angioblastic,Meningioma, Angiomatous,Meningioma, Benign,Meningioma, Cerebral Convexity,Meningioma, Clear Cell,Meningioma, Fibrous,Meningioma, Hemangioblastic,Meningioma, Hemangiopericytic,Meningioma, Intracranial,Meningioma, Intraorbital,Meningioma, Intraventricular,Meningioma, Malignant,Meningioma, Meningotheliomatous,Meningioma, Microcystic,Meningioma, Multiple,Meningioma, Olfactory Groove,Meningioma, Papillary,Meningioma, Parasagittal,Meningioma, Posterior Fossa,Meningioma, Psammomatous,Meningioma, Secretory,Meningioma, Sphenoid Wing,Meningioma, Spinal,Meningioma, Transitional,Meningioma, Xanthomatous,Meningiomas,Meningiomas, Angioblastic,Meningiomas, Angiomatous,Meningiomas, Benign,Meningiomas, Cerebral Convexity,Meningiomas, Clear Cell,Meningiomas, Fibrous,Meningiomas, Hemangioblastic,Meningiomas, Hemangiopericytic,Meningiomas, Intracranial,Meningiomas, Intraorbital,Meningiomas, Intraventricular,Meningiomas, Malignant,Meningiomas, Meningotheliomatous,Meningiomas, Microcystic,Meningiomas, Olfactory Groove,Meningiomas, Papillary,Meningiomas, Parasagittal,Meningiomas, Posterior Fossa,Meningiomas, Psammomatous,Meningiomas, Secretory,Meningiomas, Sphenoid Wing,Meningiomas, Spinal,Meningiomas, Transitional,Meningiomas, Xanthomatous,Meningiomatoses,Meningotheliomatous Meningiomas,Microcystic Meningiomas,Multiple Meningioma,Multiple Meningiomas,Olfactory Groove Meningiomas,Papillary Meningiomas,Parasagittal Meningiomas,Posterior Fossa Meningiomas,Psammomatous Meningiomas,Secretory Meningiomas,Sphenoid Wing Meningiomas,Spinal Meningiomas,Transitional Meningiomas,Wing Meningioma, Sphenoid,Wing Meningiomas, Sphenoid,Xanthomatous Meningiomas
D011372	Progestins	Compounds that interact with PROGESTERONE RECEPTORS in target tissues to bring about the effects similar to those of PROGESTERONE. Primary actions of progestins, including natural and synthetic steroids, are on the UTERUS and the MAMMARY GLAND in preparation for and in maintenance of PREGNANCY.	Gestagenic Agent,Progestagen,Progestagenic Agent,Progestational Agent,Progestational Compound,Progestational Hormone,Progestogen,Progestogens,Gestagen,Gestagen Effect,Gestagen Effects,Gestagenic Agents,Gestagenic Effect,Gestagenic Effects,Gestagens,Progestagenic Agents,Progestagens,Progestational Agents,Progestational Compounds,Progestational Hormones,Progestin,Progestin Effect,Progestin Effects,Progestogen Effect,Progestogen Effects,Agent, Gestagenic,Agent, Progestagenic,Agent, Progestational,Compound, Progestational,Effect, Gestagen,Effect, Gestagenic,Effect, Progestin,Effect, Progestogen,Effects, Gestagen,Effects, Gestagenic,Effects, Progestin,Effects, Progestogen,Hormone, Progestational
D011965	Receptors, Glucocorticoid	Cytoplasmic proteins that specifically bind glucocorticoids and mediate their cellular effects. The glucocorticoid receptor-glucocorticoid complex acts in the nucleus to induce transcription of DNA. Glucocorticoids were named for their actions on blood glucose concentration, but they have equally important effects on protein and fat metabolism. Cortisol is the most important example.	Corticoid Type II Receptor,Glucocorticoid Receptors,Glucocorticoids Receptor,Corticoid II Receptor,Corticoid Type II Receptors,Glucocorticoid Receptor,Receptors, Corticoid II,Receptors, Corticoid Type II,Receptors, Glucocorticoids,Corticoid II Receptors,Glucocorticoids Receptors,Receptor, Corticoid II,Receptor, Glucocorticoid,Receptor, Glucocorticoids
D003907	Dexamethasone	An anti-inflammatory 9-fluoro-glucocorticoid.	Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D004351	Drug Resistance	Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.	Resistance, Drug
D004963	Estrenes	Unsaturated derivatives of the ESTRANES with methyl groups at carbon-13, with no carbon at carbon-10, and with no more than one carbon at carbon-17. They must contain one or more double bonds.	19-Norandrostenes,19 Norandrostenes
D005663	Furans	Compounds with a 5-membered ring of four carbons and an oxygen. They are aromatic heterocycles. The reduced form is tetrahydrofuran.	Tetrahydrofurans
D005938	Glucocorticoids	A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system.	Glucocorticoid,Glucocorticoid Effect,Glucorticoid Effects,Effect, Glucocorticoid,Effects, Glucorticoid