Artículo

La versión final de este artículo es de uso interno de la institución.
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

In the rat, the conformationally highly befit steroid 21-hydroxy-6,19- oxidoprogesterone efficiently displaces [3H]corticostetone from thymus- glucocorticoid receptors and blocks type II receptors in kidney cytosols but competes with neither [3H]aldosterona for kidney-mineralocorticoid receptors nor [3H]progesterone for uterus-progesterone receptors. It evokes Na+ retention only at very high doses (~100 μg/100 g of rat weight) and is unable to induce tyrosine aminotransferase or to increase glycogen deposits in rat liver. When coincubated with corticostarone or dexamethasone, 2.5 μM 21OH-6OP inhibits 80% of tyrosine, aminotransferase induction. It may therefore be used experimentally as an antiglucocorticoid virtually lacking mineralocorticoid or glucocorticoid properties as well as affinity for mineralocorticoid or progesterone receptors.

Registro:

Documento: Artículo
Título:21-hydroxy-6,19-oxidoprogesterone: A novel synthetic steroid with specific antiglucocorticoid properties in the rat
Autor:Vicent, G.P.; Monteserín, M.C.; Veleiro, A.S.; Burton, G.; Lantos, C.P.; Galigniana, M.D.
Filiación:Departemento de Quim. Biol., Ciudad Universitaria, (1428) Buenos Aires, Argentina
Departemento de Quim. Organ., Ciudad Universitaria, (1428) Buenos Aires, Argentina
Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, PRHOM-Consejo Nac. Invest. Cie. y T., (1428) Buenos Aires, Argentina
Department of Pharmacology, University of Michigan, Medical School, Ann Arbor, MI 48109-0632, United States
Departemento de Quim. Biol., Ciudad Universitaria, Pabellón 2, 1428 Buenos Aires, Argentina
Palabras clave:11beta,17beta dihydroxy 6 methyl 17alpha (1 propynyl)androsta 1,4,6 trien 3 one; 15beta,16beta methylenemexrenone; 21 hydroxy 6,19 oxidoprogesterone; aldosterone; corticosterone; dexamethasone; glucocorticoid antagonist; glucocorticoid receptor; mineralocorticoid receptor; progesterone; steroid; tyrosine aminotransferase; unclassified drug; animal tissue; article; controlled study; cytosol; dose response; drug conformation; drug receptor binding; enzyme induction; kidney cell; male; nonhuman; priority journal; rat; sodium retention
Año:1997
Volumen:52
Número:4
Página de inicio:749
Página de fin:753
DOI: http://dx.doi.org/10.1124/mol.52.4.749
Título revista:Molecular Pharmacology
Título revista abreviado:MOL. PHARMACOL.
ISSN:0026895X
CODEN:MOPMA
CAS:11beta,17beta dihydroxy 6 methyl 17alpha (1 propynyl)androsta 1,4,6 trien 3 one, 74915-64-3; 15beta,16beta methylenemexrenone, 84542-26-7; aldosterone, 52-39-1, 6251-69-0; corticosterone, 50-22-6; dexamethasone, 50-02-2; progesterone, 57-83-0; tyrosine aminotransferase, 9014-55-5
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0026895X_v52_n4_p749_Vicent

Referencias:

  • Hollemberg, S.M., Weinberger, C., Ong, E.S., Cereli, G., Oro, A., Lebo, R., Thompson, E.B., Evans, R.M., Primary structure and expression of a functional human glucocorticoid receptor cDNA (1985) Nature (Lond.), 318, pp. 635-641
  • Forman, B.M., Evans, R.M., Nuclear hormone receptors activate direct, inverted, and everted repeats (1995) Ann. N. Y. Acad. Sci., 761, pp. 29-37
  • Lantos, C.P., Burton, G., Roldán, A., Damasco, M.C., Aragonés, A., Structure-activity relationship in certain glucocorticoids and mineralocorticoids (1981) Physiopathology of Endocrine Diseases and Mechanisms of Hormone Action, pp. 477-494. , (R. J. Soto, A. de Nicola, and J. Blaquier, eds.). Alan R. Liss, New York
  • Duax, W.L., Cody, V., Griffin, J.F., Rohrer, D.C., Weeks, C.M., Molecular conformation and protein binding affinity of progestins (1978) J. Toxicol. Environ. Health, 4, pp. 205-227
  • Burton, G., Galigniana, M.D., De Lavallaz, S., Brachet-Cota, A.L., Sproviero, E.M., Ghini, A.A., Lantos, C.P., Damasco, M.C., Sodium-retaining activity of some natural and synthetic 21-deoxysteroids (1995) Mol. Pharmacol., 47, pp. 535-543
  • Arriza, J., Weinberg, C., Cerelli, G., Glaser, T., Handelin, B., Housman, D., Evans, R., Cloning of human mineralocorticoid receptor complementary DNA: Structural and functional kinship with the glucocorticoid receptor (1987) Science (Washington D. C.), 237, pp. 268-275
  • Teutsch, G., Nique, F., Lemoine, G., Bouchoux, F., Cérède, E., Gofflo, D., Philibert, D., General structure-activity correlations of antihormones (1995) Ann. N. Y. Acad. Sci., 761, pp. 5-28
  • Grill, H.J., Nickisch, K., Schulze, P.E., Laurent, H., Elger, W., Heubner, A., Pollow, K., 3H-ZK91587: A new synthetic, highly specific ligand for mineralocorticoid receptor determination (1985) J. Steroid Biochem., 23 (SUPPL.), pp. 19S
  • Sutanto, W., De Kloet, E.R., ZK91587: A novel synthetic antimineralocorticoid displays high affinity for corticosterone (Type I) receptors in the rat hippocampus (1988) Life Sci, 43, pp. 1537-1543
  • Antiprogestins/antiglucocorticoids (1993) Endocrinology at Roussel-Udaf, p. 64
  • Spitz, I.M., Bardin, C.W., Mefiprestone (RU486): A modulator of progestin and glucocorticoid action (1993) N. Engl. J. Med., 329, pp. 404-412
  • Brachet-Cota, A.L., Burton, G., An improved preparation of 11,19-oxidopregn-4-ene-3,20-dione and 6,19-oxidopregnan-4-ene-3,11,20-trione (1990) Z. Naturforsch. Teil B Anorg. Chem. Org. Chem., 45, pp. 711-715
  • Veleiro, A.S., Nevado, M.V., Monteserín, M.C., Burton, G., Syntheses of 21-hydroxy-11,19-oxidopregn-4-ene-3,20-dione and 21-hydroxy-6,19-oxidopregn-4-ene-3,20-dione (1995) Steroids, 60, pp. 268-271
  • Galigniana, M.D., Vicent, G.P., Burton, G., Lantos, C.P., Features of the shuttle pair 11β-hydroxyprogesterone/11-ketoprogesterone (1997) Steroids, 62, pp. 358-364
  • Galigniana, M.D., Stability study on renal type I mineralocorticoid receptor (1996) Life Sci., 59, pp. 511-521
  • Jordan, V.C., Dix, C.J., Effect of oestradiol benzoate, tamoxifen and monohydroxytamoxifen on immature rat uterine progesterone receptor synthesis and endometrial cell division (1979) J Steroid Biochem., 11, pp. 285-291
  • Krisman, C., A method for the colorimetric estimation of glycogen with iodine (1962) Anal. Biochem., 4, pp. 17-23
  • Fry, J., Jones, C., Webkin, P., Bridges, J., The enzymatic isolation of adult rat hepatocytes in a functional and viable state (1976) Anal. Biochem., 71, pp. 341-350
  • Granner, D., Tomkins, G., Metabolism of amino acids and amines: Tyrosine amino-transferase (1975) Methods Enzymol., 17, pp. 633-637
  • Gomez-Sanchez, C.E., Gomez-Sanchez, E.P., RU26988: A new tool for the study of the mineralocorticoid receptor (1983) Endocrinology, 113, pp. 1004-1009
  • Funder, J.W., Glucocorticoid receptors (1992) J. Steroid Biochem. Mol. Biol., 43, pp. 389-394
  • Galigniana, M.D., Vicent, G.P., Lantos, C.P., Burton, G., Ligand properties of 11,19-oxidoprogesterone: A preliminary report (1993) Ann. Assoc. Química Argentina, 81, pp. 333-340
  • Krozowski, Z.S., Funder, J.F., Renal mineralocorticoid receptors and hippocampal corticosterone binding species have identical intrinsic steroid specificity (1983) Proc. Natl. Acad. Sci. USA, 80, pp. 6056-6060
  • Kraujelis, K., Ulinskaite, A., Meilus, V., Transcortin in rat kidney: Subcellular distribution of transcortin-synthesizing polyribosomes (1991) J. Steroid Biochem. Mol. Biol., 38, pp. 43-47
  • Jensen, E.V., Steroid hormone antagonists: An overview (1995) Ann. N. Y. Acad. Sci., 761, pp. 1-1
  • Hendry, L.B., Chu, C.K., Rosser, M.L., Copland, J.A., Wood, J.C., Mahesh, V.B., Design of novel antiestrogens (1994) J. Steroid Biochem. Mol. Biol., 49, pp. 269-280

Citas:

---------- APA ----------
Vicent, G.P., Monteserín, M.C., Veleiro, A.S., Burton, G., Lantos, C.P. & Galigniana, M.D. (1997) . 21-hydroxy-6,19-oxidoprogesterone: A novel synthetic steroid with specific antiglucocorticoid properties in the rat. Molecular Pharmacology, 52(4), 749-753.
http://dx.doi.org/10.1124/mol.52.4.749
---------- CHICAGO ----------
Vicent, G.P., Monteserín, M.C., Veleiro, A.S., Burton, G., Lantos, C.P., Galigniana, M.D. "21-hydroxy-6,19-oxidoprogesterone: A novel synthetic steroid with specific antiglucocorticoid properties in the rat" . Molecular Pharmacology 52, no. 4 (1997) : 749-753.
http://dx.doi.org/10.1124/mol.52.4.749
---------- MLA ----------
Vicent, G.P., Monteserín, M.C., Veleiro, A.S., Burton, G., Lantos, C.P., Galigniana, M.D. "21-hydroxy-6,19-oxidoprogesterone: A novel synthetic steroid with specific antiglucocorticoid properties in the rat" . Molecular Pharmacology, vol. 52, no. 4, 1997, pp. 749-753.
http://dx.doi.org/10.1124/mol.52.4.749
---------- VANCOUVER ----------
Vicent, G.P., Monteserín, M.C., Veleiro, A.S., Burton, G., Lantos, C.P., Galigniana, M.D. 21-hydroxy-6,19-oxidoprogesterone: A novel synthetic steroid with specific antiglucocorticoid properties in the rat. MOL. PHARMACOL. 1997;52(4):749-753.
http://dx.doi.org/10.1124/mol.52.4.749