Ações genômicas e não genômicas dos hormônios esteroides

Autores

  • Bruno Damião Universidade Federal de Alfenas (UNIFAL-MG) e Faculdade de Americana (FAM)
  • Carla Miguel Oliveira Universidade Federal de Alfenas
  • Maria Rita Rodrigues Universidade Federal de Alfenas

Resumo

Os hormônios esteroides são importantes mantenedores da homeostase corporal humana, além de possuírem papéis importantes no desenvolvimento e maturação dos órgãos do feto e controlarem os ciclos reprodutivos masculinos e femininos. Os esteroides humanos são produzidos a partir de um precursor comum, o colesterol, em células endócrinas especializadas, como os testículos, os ovários e as glândulas adrenais. A testosterona, o estrógeno, o cortisol e a aldosterona são alguns exemplos de hormônios esteroides mais conhecidos. O mecanismo de ação comum dos esteroides é o genômico, que ocorre através da ligação destes hormônios com receptores intracelulares, que são fatores de transcrição dependentes de ligantes, afetando a transcrição gênica da célula. Porém, alguns efeitos fisiológicos rápidos não conseguem ser explicados pelo modelo tradicional de ação, visto que alterações no processo de transcrição gênica levam um determinado tempo para surtirem efeito. Assim, estuda-se hoje os efeitos não-genômicos dos esteroides, que incluem ações na membrana celular, onde alteram a abertura de canais iônicos e seus efeitos cardiovasculares. O artigo em questão também aborda o modelo de ação em dois passos dos hormônios esteroides, com enfoque nos hormônios reprodutivos e na vitamina D.

Biografia do Autor

Bruno Damião, Universidade Federal de Alfenas (UNIFAL-MG) e Faculdade de Americana (FAM)

Professor, Biomédico, Biólogo licenciado, Mestre em neurociências e comportamento e Doutorando em ciências farmacêuticas.

Referências

ALLÉRA, A; WILDT, L. Glucocorticoid-recognizing and-effector sites in rat liver plasma membrane. Kinetics of corticosterone uptake by isolated membrane vesicles—II. Comparative influx and efflux. The Journal of steroid biochemistry and molecular biology, v. 42, n. 7, p. 757-771, 1992.

BARAN, D.T. Annexin II is the membrane receptor that mediates the rapid actions of 1α, 25‐dihydroxyvitamin D3. Journal of cellular biochemistry, v. 78, n. 1, p. 34-46, 2000.

BASARIA, S.; WAHLSTROM, J. T.; DOBS, A. S. Clinical review 138: anabolic– androgenic steroid therapy in the treatment of chronic diseases. J. Clin. Endocrinol. Metab, v. 86, p. 5108–5117, 2001.

BEATO, M.; KLUG, J. Steroid hormone receptors: an update. Human reproduction update, v. 6, n. 3, p. 225-236, 2000.

BIRD, A.D.; MCDOUGALL, A.R.; SEOW, B.; HOOPER, S.B.; COLE, T.J. Minireview: glucocorticoid regulation of lung development: lessons learned from conditional GR knockout mice. Molecular Endocrinology, 29(2), 158-171, 2015.

BUNONE, G. et al. Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation. The EMBO journal, v. 15, n. 9, p. 2174, 1996.

CHRIST, M.; WEHLING, M. Cardiovascular steroid actions: swift swallows or sluggish snails?. Cardiovascular research, v. 40, n. 1, p. 34-44, 1998.

CLARKE, C.H. et al. Perimembrane localization of the estrogen receptor α protein in neuronal processes of cultured hippocampal neurons. Neuroendocrinology, v. 71, n. 1, p. 34-42, 2000.

CLARK, A. S.; HERNDERSON, L. P. Behavioral and physiological responses to anabolic-androgenic steroids. NeurosciBiobehav Rev., v. 27, n.5, p. 413-436, 2003.

COLE, T. J.; SHORT, K. L.; HOOPER, S.B. The science of steroids. Seminars in Fetal and Neonatal Medicine. WB Saunders, p. 170-175, 2019.

CONWAY, A. J. et al. Use, misuse and abuse of androgens. The Endocrine Society of Australia consensus guidelines for androgen prescribing. Med J Aust, v. 172, p. 220-224, 2000.

DEFRANCO, D.B. Role of molecular chaperones in subnuclear trafficking of glucocorticoid receptors. Kidney international, v. 57, n. 4, p. 1241-1249, 2000.

DOTSON, J. L.; BROWN, R. T. The history of the development of anabolic-androgenic steroids. Pediatric Clinics of North America, v. 54, n. 4, p. 761-769, 2007.

EDELMAN, I. S. Mechanism of action of steroid hormones. Journal of steroid biochemistry, v. 6, n. 3-4, p. 147-159, 1975.

ENDOH, H. et al. Rapid activation of MAP kinase by estrogen in the bone cell line. Biochemical and biophysical research communications, v. 235, n. 1, p. 99-102, 1997.

FALKENSTEIN, E. et al. Multiple actions of steroid hormones—a focus on rapid, nongenomic effects. Pharmacological reviews, v. 52, n. 4, p. 513-556, 2000.

FIORETTI, F.M. Revising the role of the androgen receptor in breast cancer. Journal of molecular endocrinology, v. 52, n. 3, p. R257-R265, 2014.

GU, Q.; KORACH, K.S.; MOSS, R. L. Rapid action of 17β-estradiol on kainate-induced currents in hippocampal neurons lacking intracellular estrogen receptors. Endocrinology, v. 140, n. 2, p. 660-666, 1999.

HATTANGADY, N.G.; OLALA, L.O.; BOLLAG, W.B.; RAINEY, W.E. Acute and chronic regulation of aldosterone production. Molecular and cellular endocrinology, v. 350, n. 2, p. 151-162, 2012.

HENRICH, V.C.; BROWN, N.E. Insect nuclear receptors: a developmental and comparative perspective. Insect biochemistry and molecular biology, v. 25, n. 8, p. 881-897, 1995.

HENDRY, L.B. Stereochemical complementarity of DNA and steroid agonists and antagonists. Journal of steroid biochemistry, v. 31, n. 4, p. 493-523, 1988.

HOLICK, M. F. The vitamin D epidemic and its health consequences. The Journal of nutrition, v. 135, n. 11, p. 2739S-2748S, 2005.

KENNEDY, M. C. Newer drugs used to enhance sporting performance. Med J Aust, v. 173, p. 314-317, 2000.

LIM-TIO, S.S.; KEIGHTLEY, M.C.; FULLER, P.J. Determinants of specificity of transactivation by the mineralocorticoid or glucocorticoid receptor. Endocrinology, v. 138, n. 6, p. 2537-2543, 1997.

LUCAS-HERALD, A.K. Genomic and non-genomic effects of androgens in the cardiovascular system: clinical implications. Clinical Science, v. 131, n. 13, p. 1405-1418, 2017.

LUISI, B.F.; XU, W.; OTWINOWSKI, Z.; FREEDMAN, L.P.; YAMAMOTO, K.R.; SIGLER, P.B. Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA. Nature, 352(6335), 497-505, 1991

LUCONI, M. et al. Identification and characterization of a novel functional estrogen receptor on human sperm membrane that interferes with progesterone effects. The Journal of Clinical Endocrinology & Metabolism, v. 84, n. 5, p. 1670-1678, 1999.

LUSETTI, M.; LICATA, M.; SILINGARDI, E.; BONETTI, L.R. Pathological changes in anabolic androgenic steroid users. Journal of Forensic and Legal Medicine. V.33, p.101-104, 2015.

MAJEWSKA, M.D. et al. Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science, v. 232, n. 4753, p. 1004-1007, 1986.

MANGELSDORF, D.J.; EVANS, R.M. The RXR heterodimers and orphan receptors. Cell, v. 83, n. 6, p. 841-850, 1995.

MEHTA, A.K.; TICKU, M.K. An investigation on the role of nitric oxide in the modulation of the binding characteristics of various radioligands of GABA A receptors by 5α-pregnan-3α-ol-20-one in the rat brain regions. Brain research, v. 832, n. 1, p. 164-167, 1999.

MHILLAJ, E.; MORGESE, M.G.; TUCCI, P.; BONE, M. Effects of anabolic androgens on brain reward function. Front. Neurosci. V.9, p.295-302, 2015.

MIGLIACCIO, A. et al. Activation of the Src/p21 ras/Erk pathway by progesterone receptor via cross‐talk with estrogen receptor. The EMBO journal, v. 17, n. 7, p. 2008-2018, 1998.

MISRA, M. et al. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics, v. 122, n. 2, p. 398-417, 2008.

MOYER, M. L. et al. Modulation of cell signaling pathways can enhance or impair glucocorticoid-induced gene expression without altering the state of receptor phosphorylation. Journal of Biological Chemistry, v. 268, n. 30, p. 22933-22940, 1993.

MÜLLER, Dominik N.; KLEINEWIETFELD, Markus; KVAKAN, Heda. Vitamin D review. Journal of the Renin-Angiotensin-Aldosterone System, v. 12, n. 2, p. 125-128, 2011.

NORDEEN, S.K.; MOYER, M.L.; BONA, B.J. The coupling of multiple signal transduction pathways with steroid response mechanisms. Endocrinology, v. 134, n. 4, p. 1723-1732, 1994.

OÑATE, S.A. et al. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science, v. 270, n. 5240, p. 1354-1358, 1995.

PAGONIS, T.A.; ANGELOPOULOS, N.V.; KOUKOULIS, G.N.; HADJICHRISTODOULOU, C.S. Psychiatric side effects induced by supraphysiological doses of combinations of anabolic steroids correlate to the severity of abuse. European Psychiatry, v. 21(8), p. 551-562, 2006.

PAPPAS, T.C.; GAMETCHU, B.; WATSON, C.S. Membrane estrogen receptors identified by multiple antibody labeling and impeded-ligand binding. The FASEB Journal, v. 9, n. 5, p. 404-410, 1995

PAYNE, A.H.; HALES, D.B. Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocrine reviews, v. 25, n. 6, p. 947-970, 2004.

PIETRAS, R.J.; SZEGO, C.M. Cell membrane estrogen receptors resurface. Nature medicine, v. 5, n. 12, p. 1330-1330, 1999.

POMARA, C.; NERI, M.; BELLO, S.; FIORI, C. Neurotoxicity by synthetic androgen steroids: oxidative stress, apoptosis, and neuropathology: a review. Current Neuropharmacology. V.13, p.132-145, 2015.

PRATT, W.B.; TOFT, D.O. Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocrine reviews, v. 18, n. 3, p. 306-360, 1997.

RAY, A.; PREFONTAINE, K.E. Physical association and functional antagonism between the p65 subunit of transcription factor NF-kappa B and the glucocorticoid receptor. Proceedings of the National Academy of Sciences, v. 91, n. 2, p. 752-756, 1994.

ROBERTSON, H.M.; ZUMPANO, K.L. Molecular evolution of an ancient mariner transposon, Hsmarl, in the human genome. Gene, v. 205, n. 1, p. 203-217, 1997.

SANTOS, A. M. Mundo Anabólico. Editora Manole Ltda, 2007.

SHAHIDI, N. T. A review of chemistry, biological action and clinical applications of anabolic androgenic steroid. Clin. Ther., v. 23, p. 1355-1390, 2001.

SILVA, P.R.P. Prevalência do uso de agentes anabólicos em praticantes de musculação de Porto Alegre. Arq Bras Endocrinol Metab, São Paulo , v. 51, n. 1, p. 104-110, 2007.

STILGER, V. G.; YESALIS, C. E. Anabolic–androgenic steroid use among high school football players. J Community Health, v. 24, n. 2, p. 131-145, 1999.

SWAIN, L.D. et al. Nongenomic regulation of chondrocyte membrane fluidity by 1, 25-(OH) 2D3 and 24, 25-(OH) 2D3 is dependent on cell maturation. Bone, v. 14, n. 4, p. 609-617, 1993.

TORAN-ALLERAND, C.D.; SINGH, M.; SÉTÁLÓ, G. Novel mechanisms of estrogen action in the brain: new players in an old story. Frontiers in neuroendocrinology, v. 20, n. 2, p. 97-121, 1999.

WEATHERMAN, R.V.; FLETTERICK, R.J.; SCANLAN, T.S. Nuclear-receptor ligands and ligand-binding domains. Annual review of biochemistry, v. 68, n. 1, p. 559-581, 1999.

WETZEL, C.H.R.; VEDDER, H.; HOLSBOER, F.; ZIEGLGÄNSBERGER, W.; DEISZ, R.A. Bidirectional effects of the neuroactive steroid tetrahydrodeoxycorticosterone on GABA‐activated Cl− currents in cultured rat hypothalamic neurons. British journal of pharmacology, 127(4), 863-868, 1999.

WILSON, H.; LIPSETT, M.B.; RYAN, D.W. Urinary excretion of Δ5-pregnenetriol and other 3β-hydroxy-Δ5 steroids by subjects with and without endocrine disease. The Journal of Clinical Endocrinology & Metabolism, v. 21, n. 10, p. 1304-1320, 1961.

ZANNAD, F. Eplerenone in patients with systolic heart failure and mild symptoms. New England Journal of Medicine, v. 364, n. 1, p. 11-21, 2011.

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Publicado

31-12-2019

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Damião, B., Oliveira, C. M., & Rodrigues, M. R. (2019). Ações genômicas e não genômicas dos hormônios esteroides. Revista Farmácia Generalista Generalist Pharmacy Journal, 1(2), 46–66. Recuperado de https://publicacoes.unifal-mg.edu.br/revistas/index.php/revistafarmaciageneralista/article/view/1093

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