Artículo

Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

The physiological importance of and therapeutic interest in dehydroepiandrosterone (DHEA) has been predominantly in relation to its action as an inhibitor of the promotion and progression of several kinds of tumours, including those of breast, prostate, lung, colon, liver and skin tissues. The aim of the present study was to determine the role of DHEA in diethylstilboestrol (DES)-induced pituitary hyperplasia. Female Sprague-Dawley rats were divided into four treatment groups: DES (implanted s.c. with a 20 mg DES pellet), DHEA (two 50 mg DHEA pellets), DHEA/DES (both DHEA and DES pellets), and controls (not implanted). Every week, all rats were weighed and cycled, and jugular blood samples were obtained. After 7 weeks, rats were killed. Hypophyses were removed and weighed, and serum prolactin, GH, IGF-I and leptin levels were assayed by RIA. DHEA cotreatment reduced pituitary enlargement by 39% in DES-treated rats. It also reduced the hyperprolactinaemia (280.4 ± 43.6 ng/ml for DHEA/DES vs 823.5 ± 127.1 ng/ml for DES) and partially reversed the loss of body weight induced by DES. DHEA treatment did not modify the effects of DES on serum GH, IGF-I and leptin levels. But DHEA per se also increased pituitary weight and induced hyperprolactinaemia, although to a lesser degree than DES. We conclude that DHEA administration has beneficial effects on oestrogen-induced pituitary hyperplasia and hyperprolactinaemia, but the fact that DHEA per se also induces diverse hormonal effects and a slight pituitary enlargement limits its use as a possible therapeutic drug.

Registro:

Documento: Artículo
Título:Dehydroepiandrosterone treatment attenuates oestrogen-induced pituitary hyperplasia
Autor:Suárez, C.; García Tornadú, I.; Khalil, W.; Becu-Villalobos, D.
Filiación:Inst. de Biol. y Med. Experimental, CONICET V, Obligado 2490, 1428 Buenos Aires, Argentina
Palabras clave:diethylstilbestrol; estrogen; growth hormone; leptin; prasterone; prolactin; somatomedin C; animal experiment; article; blood sampling; breast tumor; cancer inhibition; colon tumor; controlled study; drug implant; female; growth hormone blood level; hormone action; hyperplasia; hyperprolactinemia; hypophysis disease; liver tumor; lung tumor; nonhuman; priority journal; prolactin blood level; prostate tumor; radioimmunoassay; rat; rat strain; skin tumor; weight reduction; Animals; Dehydroepiandrosterone; Diethylstilbestrol; Female; Growth Hormone; Hyperplasia; Insulin-Like Growth Factor I; Leptin; Models, Animal; Organ Size; Pituitary Gland; Prolactin; Rats; Rats, Sprague-Dawley
Año:2002
Volumen:174
Número:3
Página de inicio:447
Página de fin:454
DOI: http://dx.doi.org/10.1677/joe.0.1740447
Título revista:Journal of Endocrinology
Título revista abreviado:J. Endocrinol.
ISSN:00220795
CODEN:JOENA
CAS:Dehydroepiandrosterone, 53-43-0; Diethylstilbestrol, 56-53-1; Growth Hormone, 9002-72-6; Insulin-Like Growth Factor I, 67763-96-6; Leptin; Prolactin, 9002-62-4
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00220795_v174_n3_p447_Suarez

Referencias:

  • Arimura, A., Smith, W., Schally, A., Blockade of the stress-induced decrease in blood GH by antisomatostatin serum in rats (1976) Endocrinology, 98, pp. 540-543
  • Arlt, W., Callies, F., Allolio, B., DHEA replacement in women with adrenal insufficiency: Pharmacokinetics, bioconversion and clinical effects on well-being, sexuality and cognition (2000) Endocrine Research, 26, pp. 505-511
  • Boccuzzi, G., Aragno, M., Brignardello, E., Tamagno, E., Conti, G., Di Monaco, M., Racca, S., Di Carlo, F., Opposite effects of dehydroepiandrosterone on the growth of 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinomas (1992) Anticancer Research, 12, pp. 1479-1483
  • Boccuzzi, G., Di Monaco, M., Brignardello, E., Leonardi, L., Gatto, V., Pizzini, A., Gallo, M., Dehydroepiandrosterone antiestrogenic action through androgen receptor in MCF-7 human breast cancer cell line (1993) Anticancer Research, 13, pp. 2267-2272
  • Borski, R.J., Tsai, W., DeMott-Friberg, R., Barkan, A.L., Regulation of somatic growth and the somatotropic axis by gonadal steroids: Primary effect on insulin-like growth factor I gene expression and secretion (1996) Endocrinology, 137, pp. 3253-3259
  • Brann, D.W., De Sevilla, L., Zamorano, P.L., Mahesh, V.B., Regulation of leptin gene expression and secretion by steroid hormones (1999) Steroids, 64, pp. 659-663
  • Bray, M.J., Vick, T.M., Shah, N., Anderson, S.M., Rice, L.W.I.A., Evans, R.M., Veldhuis, J.D., Short-term estradiol replacement in postmenopausal women selectively mutes somatostatin's dose-dependent inhibition of fasting growth hormone secretion (2001) Journal of Clinical Endocrinology and Metabolism, 86, pp. 3143-3149
  • Cleary, M., The antiobesity effects of DHEA in rats (1991), 196, pp. 8-16. , Proceedings of the Society for Experimental Biology and Medicine; De Nicola, A.F., von Lawzewitsch, I., Kaplan, S.E., Libertun, C., Biochemical and ultrastructural studies on estrogen-induced pituitary tumors in F344 rats (1978) Journal of the National Cancer Institute, 61, pp. 753-763
  • Diaz-Torga, G.S., Gonzalez Iglesias, A., Achaval-Zaia, R., Libertun, C., Becu-Villalobos, D., Angiotensin II induced calcium mobilization and prolactin release in normal and hyperplastic pituitary cells (1998) American Journal of Physiology, 274, pp. E534-E540
  • Diaz-Torga, G., Feierstein, C., Libertun, C., Gelman, D., Kelly, M.A., Low, M.J., Rubinstein, M., Becu-Villalobos, D., Disruption of the D2 dopamine receptor alters GH and IGF-I secretion and causes dwarfism in male mice (2002) Endocrinology, 143, pp. 1270-1279
  • Ebeling, P., Koivisto, V.A., Physiological importance of dehydroepiandrosterone (1994) Lancet, 343, pp. 1479-1481
  • Frye, C.A., Lacey, E.H., The neurosteroids DHEA and DHEAS may influence cognitive performance by altering affective state (1999) Physiology and Behavior, 66, pp. 85-92
  • Gansler, T.S., Muller, S., Cleary, M.P., Chronic administration of dehydroepiandrosterone reduces pancreatic beta-cell hyperplasia and hyperinsulinemia in genetically obese Zucker rats (1985), 180, pp. 155-162. , Proceedings of the Society for Experimental Biology and Medicine; Gatto, V., Aragno, M., Gallo, M., Tamagno, E., Martini, A., Dimonaco, M., Brignardello, E., Boccuzzi, G., Dehydroepiandrosterone inhibits the growth of DMBA-induced rat mammary carcinoma via the androgen receptor (1998) Oncology Reports, 5, pp. 241-243
  • Gonzalez Iglesias, A., Diaz-Torga, G., Piroli, G., Achaval-Zaia, R., De Nicola, A.F., Libertun, C., Becu-Villalobos, D., Bromocriptine restores angiotensin II response in pituitary hyperplasia (2000) Molecular and Cellular Endocrinology, 165, pp. 67-74
  • Hertz, P., Silbermann, L.E., Even, L., Hochberg, Z., Effects of sex steroid on the response of cultured rat pituitary cells to growth hormone-releasing hormone and somatostatin (1989) Endocrinology, 125, pp. 581-585
  • Hinson, J.P., Raven, P.W., DHEA deficiency syndrome: A new term for old age? (1999) Journal of Endocrinology, 163, pp. 1-5
  • Hu, Y., Cardounel, A., Gursoy, E., Anderson, P., Kalimi, M., Anti-stress effects of dehydroepiandrosterone: Protection of rats against repeated immobilization stress-induced weight loss, glucocorticoid receptor production, and lipid peroxidation (2000) Biochemical Pharmacology, 59, pp. 753-762
  • Jarrar, D., Wang, P., Cioffi, W.G., Bland, K.I., Chaudry, I.H., Mechanisms of the salutary effects of dehydroepiandrosterone after trauma-hemorrhage: Direct or indirect effects on cardiac and hepatocellular functions? (2000) Archives of Surgery, 135, pp. 416-423
  • Knudsen, J.F., Costoff, A., Mahesh, V.B., Dehydroepiandrosterone induced polycystic ovaries and acyclicity in the rat (1975) Fertility and Sterility, 26, pp. 807-817
  • Kroboth, P.D., Salek, F.S., Pittenger, A.L., Fabian, T.J., Frye, R.F., DHEA and DHEA-S: A review (1999) Journal of Clinical Pharmacology, 39, pp. 327-348
  • Labrie, F., Diasmond, P., Cusan, L., Gomez, J.L., Belanger, A., Candas, B., Effect of 12-month dehydroepiandrosterone replacement therapy on bone, vagina, and endometrium in postmenopausal women (1997) Journal of Clinical Endocrinology and Metabolism, 82, pp. 3498-3505
  • Lacau-Mengido, I.M., Mejía, M., Diaz-Torga, G., Gonzalez Iglesias, A., Formía, N., Libertun, C., Becu-Villalobos, D., Endocrine studies in ivermectin-treated heifers from birth to puberty (2000) Journal of Animal Science, 78, pp. 1-8
  • Ladriere, L., Laghmich, A., Malaisse-Lagae, F., Malaisse, W.J., Effect of dehydroepiandrosterone in hereditarily diabetic rats (1997) Cellular and Biochemical Function, 15, pp. 287-292
  • Lardy, H., Partridge, B., Kneer, N., Wei, Y., Ergosteroids: Induction of thermogenic enzymes in liver of rats treated with steroids derived from dehydroepiandrosterone (1995) PNAS, 92, pp. 6617-6619
  • Li, K., Foo, T., Adams, J.B., Products of dehydroepiandrosterone metabolism by human mammary tumors and their influence on estradiol receptor binding (1978) Steroids, 31, pp. 113-127
  • Maggiolini, M., Donzé, O., Jeannin, E., Andò, S., Didier, P., Adrenal androgens stimulate the proliferation of breast cancer cells as direct activators of estrogen receptor α (1999) Cancer Research, 59, pp. 4864-4869
  • McIntosh, M., Bao, H., Lee, C., Opposing actions of dehydroepiandrosterone and corticosterone in rats (1999), 221, pp. 198-206. , Proceedings of the Society for Experimental Biology and Medicine; Morales, A., Nolan, J., Nelson, J., Yen, S., Effects of replacement dose of DHEA in men and women of advancing age (1994) Journal of Clinical Endocrinology and Metabolism, 78, pp. 1360-1367
  • Müller, E., Locatelli, V., Cocchi, D., Neuroendocrine control of growth hormone secretion (1999) Physiological Reviews, 79, pp. 511-607
  • Nippoldt, T.B., Nair, K.S., Is there a case for DHEA replacement? (1998) Baillieres Clinical and Endocrinological Metabolism, 12, pp. 507-520
  • Nyce, J.W., Magee, P.N., Hard, G.C., Schwartz, A.G., Inhibition of 1,2-dimethylhydrazine-induced colon tumorigenesis in Balb/c mice by dehydroepiandrosterone (1984) Carcinogenesis, 5, pp. 57-62
  • Paolisso, G., Rizzo, M.R., Mone, C.M., Tagliamonte, M.R., Gambardella, A., Riondino, M., Carella, C., D'Onofrio, F., Plasma sex hormones are significantly associated with plasma leptin concentration in healthy subjects (2001) Clinical Endocrinology, 48, pp. 291-297
  • Parente J.A., Jr., Berdanier, C.D., Drugs that suppress hepatic fat synthesis in starved-refed BHE/cdb rats also have an effect on muscle protein synthesis (1993), 204, pp. 172-179. , Proceedings of the Society for Experimental Biology and Medicine; Pashko, L.L., Hard, G.C., Rovito, K.J., Williams, J.R., Sobel, E.L., Schwartz, A.G., Inhibition of 7,12-dimethylbenz(a)anthracene-induced skin papillomas and carcinomas by dehydroepiandrosterone and 3-beta-methylandrost-5-en-17-one in mice (1985) Cancer Research, 45, pp. 164-166
  • Pineiro, V., Casabiell, X., Peino, R., Lage, M., Camina, J.P., Menendez, C., Baltar, J., Casanueva, F., Dihydrotestosterone, stanazolol, androstenedione and dehydroepiandrosterone sulphate inhibit leptin secretion in female but not in male samples of omental adipose tissue in vitro: Lack of effect of testosterone (1999) Journal of Endocrinology, 160, pp. 425-432
  • Piroli, G., Grillo, C.A., Ferrini, M.G., Lux-Lantos, V., De Nicola, A.F., Antagonism by progesterone of diethylstilbestrol-induced pituitary tumorigenesis in Fischer 344 rats: Effects on sex steroid receptors and tyrosine hydroxylase mRNA (1996) Neuroendocrinology, 63, pp. 530-539
  • Poortman, J., Prenen, J.A.C., Schwarz, F., Thijssen, J.H.H., Interaction of delta-5-androstene-3 beta, 17 beta-diol with estradiol and dihydrotestosterone receptors in human myometrial and mammary cancer tissue (1975) Journal of Clinical Endocrinology and Metabolism, 40, pp. 373-379
  • Rao, K.V.N., Johnson, W.D., Bosland, M.C., Lubet, R.A., Steele, V.E., Kelloff, G.J., McCormick, D.L., Chemoprevention of rat prostate carcinogenesis by early and delayed administration of dehydroepiandrosterone (1999) Cancer Research, 59, pp. 3084-3089
  • Rao, M.S., Subbarao, V., Yeldandi, A.V., Reddy, J.K., Hepatocarcinogenicity of dehydroepiandrosterone in the rat (1992) Cancer Research, 52, pp. 2977-2979
  • Richards, R.J., Porter, J.R., Svec, F., Serum leptin, lipids, free fatty acids, and fat pads in long-term dehydroepiandrosterone-treated Zucker rats (2000), 223, pp. 258-262. , Proceedings of the Society for Experimental Biology and Medicine; Rose, K., Allan, A., Gauldie, S., Stapleton, G., Lorraine, D., Dott, K., Martin, C., Lathe, R., Neurosteroid hydroxylase CYP7B. Vivid reporter activity in dentate gyrus of gene-targeted mice and abolition of a widespread pathway of steroid and oxysterol hydroxylation (2001) Journal of Biological Chemistry, 276, pp. 23937-23944
  • Sarkar, D.K., Gottschall, P.E., Meites, J., Damage to hypothalamic dopaminergic neurons is associated with development of prolactin-secreting pituitary tumors (1982) Science, 218, pp. 684-686
  • Schiffelholz, T., Holsboer, F., Lancel, M., High doses of systemic DHEA-sulfate do not affect sleep structure and elicit moderate changes in non-REM sleep EEG in rats (2000) Physiology and Behavior, 69, pp. 399-404
  • Schwartz, A.G., Tannen, R.H., Inhibition of 7,12-dimethylbenz-[a]anthracene- and urethan-induced lung tumor formation in A/J mice by long-term treatment with dehydroepiandrosterone (1981) Carcinogenesis, 2, pp. 1335-1337
  • Schwartz, A.G., Fairman, D.K., Polansky, M., Lewbart, M.L., Pashko, L.L., Inhibition of 7,12-dimethylbenz[a]anthracene-initiated and 12-O-tetradecanoylphorbol-13-acetate-promoted skin papilloma formation in mice by dehydroepiandrosterone and two synthetic analogs (1989) Carcinogenesis, 10, pp. 1809-1813
  • Shepherd, A., Cleary, M.P., Metabolic alterations after dehydroepiandrosterone treatment in Zucker rats (1984) American Journal of Physiology. Endocrinology and Metabolism, 246, pp. E123-E128
  • Shulman, D.I., Sweetland, M., Duckett, G., Root, A.W., Effect of estrogen on the growth hormone secretory response to GH-releasing factor in the castrate adult female rat in vivo (1987) Endocrinology, 120, pp. 1047-1051
  • Simard, J., Vincent, A., Duchesne, R., Labrie, F., Full oestrogenic activity of C19-delta 5 adrenal steroids in rat pituitary lactotrophs and somatotrophs (1988) Molecular and Cellular Endocrinology, 55, pp. 233-242
  • Sourla, A., Martel, C., Labrie, C., Labrie, F., Almost exclusive androgenic action of dehydroepiandosterone in the rat mammary gland (1998) Endocrinology, 139, pp. 753-764
  • Svec, F., Porter, J., The actions of exogenous dehydroepiandrosterone in experimental animals and humans (1998), 218, pp. 174-191. , Proceedings of the Society for Experimental Biology and Medicine; Ward, C.W., Costoff, A., Mahesh, V.B., The induction of polycystic ovaries in mature cycling rats by the administration of dehydroepiandrosterone (DHEA) (1978) Biology of Reproduction, 18, pp. 614-623
  • Wolf, O.T., Kirschbaum, C., Actions of dehydroepiandrosterone and its sulfate in the central nervous system: Effects on cognition and emotion in animals and humans (1999) Brain Research Reviews, 30, pp. 264-288
  • Yang, J.Y., Schwartz, A.G., Henderson, E.E., Inhibition of 3′ azido-3′ deoxythymidine-resistant HIV-1 infection by dehydroepiandrosterone in vitro (1994) Biochemical and Biophysical Research Communications, 201, pp. 1424f-1432f

Citas:

---------- APA ----------
Suárez, C., García Tornadú, I., Khalil, W. & Becu-Villalobos, D. (2002) . Dehydroepiandrosterone treatment attenuates oestrogen-induced pituitary hyperplasia. Journal of Endocrinology, 174(3), 447-454.
http://dx.doi.org/10.1677/joe.0.1740447
---------- CHICAGO ----------
Suárez, C., García Tornadú, I., Khalil, W., Becu-Villalobos, D. "Dehydroepiandrosterone treatment attenuates oestrogen-induced pituitary hyperplasia" . Journal of Endocrinology 174, no. 3 (2002) : 447-454.
http://dx.doi.org/10.1677/joe.0.1740447
---------- MLA ----------
Suárez, C., García Tornadú, I., Khalil, W., Becu-Villalobos, D. "Dehydroepiandrosterone treatment attenuates oestrogen-induced pituitary hyperplasia" . Journal of Endocrinology, vol. 174, no. 3, 2002, pp. 447-454.
http://dx.doi.org/10.1677/joe.0.1740447
---------- VANCOUVER ----------
Suárez, C., García Tornadú, I., Khalil, W., Becu-Villalobos, D. Dehydroepiandrosterone treatment attenuates oestrogen-induced pituitary hyperplasia. J. Endocrinol. 2002;174(3):447-454.
http://dx.doi.org/10.1677/joe.0.1740447