Estrogen receptors: expression, regulation, signaling, and function in the male reproductive tract, breast, and brain

• Grant number: 08/56564-1
• Support Opportunities: Research Projects - Thematic Grants
• Start date: March 01, 2009
• End date: October 31, 2013
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Catarina Segreti Porto
• Grantee: Catarina Segreti Porto
• Host Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Principal investigators: Maria de Fátima Magalhães Lazari
• Associated scholarship(s): 12/02924-2 - Expression, regulation and function of estrogen receptors in androgen-independent prostate cancer cells PC-3, BP.MS; 12/02362-4 - Effects of 17beta-estradiol and their receptors in cells of testicular cancer, BP.PD; 11/14535-8 - Intracellular Signaling and function of estrogen receptors in the rat epididymis, BP.MS; 10/15808-5 - Identification, regulation and function of estrogen receptors GPER and ESR1-36 in cell lines of human normal prostate, of prostate cancer and of benign prostatic hyperplasia., BP.IC; 10/04585-5 - Analysis of anti-estrogenic drugs activity in methylation status on estrogen receptors promoters in breast cancer cell lines, BP.MS

Abstract

Estrogen plays a role in reproductive tissues both in females and in males, and also in non-reproductive tissues, including the brain. Physiological and pathophysiological effects of estrogen are mediated by three receptors (ERα, ERβ and the recent1y discovered GPR30) and include both changes in gene transcription and rapid cellular responses. The present project intends to analyze the role of estrogen in the male reproductive tract, breast, and hippocampus. We will study the expression of estrogen receptors in normal tissues and in samples of breast tumors, before and after antiestrogen treatments, epigenetic alterations in the promoter region of the estrogen receptor genes, the proteomic analysis after exposure of cells to estrogen or antiestrogens, and functional aspects of estrogen and antiestrogens, including intracellular signaling mechanisms and effects on cell proliferation and apoptosis. Studies on the expression, regulation, intracellular signaling and function of estrogen receptors in these systems may contribute to the understanding and treatment of several pathological conditions, including male infertility, breast and prostate cancer, neurodegenerative diseases, to the development of novel male contraceptives, and to the understanding of mechanisms involved in drug-resistance during cancer therapy. (AU)

Scientific publications

(9)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERNANDES, S. A. F.; GOMES, G. R. O.; SIU, E. R.; DAMAS-SOUZA, D. M.; BRUNI-CARDOSO, A.; AUGUSTO, T. M.; LAZARI, M. F. M.; CARVALHO, H. F.; PORTO, C. S.. The anti-oestrogen fulvestrant (ICI 182,780) reduces the androgen receptor expression, ERK1/2 phosphorylation and cell proliferation in the rat ventral prostate. INTERNATIONAL JOURNAL OF ANDROLOGY, v. 34, n. 5, 1, p. 486-500, OCT 2011. (08/56564-1)

PEREIRA, M. F. N.; FERNANDES, S. A. F.; NASCIMENTO, A. R.; SIU, E. R.; HESS, R. A.; OLIVEIRA, C. A.; PORTO, C. S.; LAZARI, M. F. M.. Effects of the oestrogen receptor antagonist Fulvestrant on expression of genes that affect organization of the epididymal epithelium. ANDROLOGY, v. 2, n. 4, p. 559-571, JUL 2014. (08/56564-1)

FERNANDES, S. A. F.; GOMES, G. R. O.; SIU, E. R.; DAMAS-SOUZA, D. M.; BRUNI-CARDOSO, A.; AUGUSTO, T. M.; LAZARI, M. F. M.; CARVALHO, H. F.; PORTO, C. S.. The anti-oestrogen fulvestrant (ICI 182,780) reduces the androgen receptor expression, ERK1/2 phosphorylation and cell proliferation in the rat ventral prostate. INTERNATIONAL JOURNAL OF ANDROLOGY, v. 34, n. 5, p. 15-pg., 2011-10-01. (08/56564-1)

DOS SANTOS PEREIRA, RENATO TAVARES; PORTO, CATARINA SEGRETI; FRANCIS ABDALLA, FERNANDO MAURICIO. Ovariectomy and 17 beta-estradiol replacement play a role on the expression of Endonuclease-G and phosphorylated cyclic AMP response element-binding (CREB) protein in hippocampus. Molecular and Cellular Endocrinology, v. 382, n. 1, p. 227-233, JAN 25 2014. (08/56564-1)

MARUYAMA, NADIA O.; LUCAS, THAIS F. G.; PORTO, CATARINA S.; ABDALLA, FERNANDO M. F.. Estrogen receptor ESR1 regulates the phospholipase C-inositol phosphate signaling in the hippocampus from rats in proestrous and estrous phases. Steroids, v. 78, n. 1, p. 8-14, JAN 2013. (08/56564-1)

MAGALHAES LAZARI, MARIA FATIMA; GAMEIRO LUCAS, THAIS FABIANA; YASUHARA, FABIANA; OLIVEIRA GOMES, GISELE RENATA; SIU, ERICA ROSANNA; ROYER, CARINE; FERREIRA FERNANDES, SHEILLA ALESSANDRA; PORTO, CATARINA SEGRETI. Estrogen receptors and function in the male reproductive system. Arquivos Brasileiros de Endocrinologia e Metabologia, v. 53, n. 8, p. 923-933, NOV 2009. (08/56564-1)

LOMBARDI, ANA PAOLA G.; PISOLATO, RAISA; VICENTE, CAROLINA M.; LAZARI, MARIA FATIMA M.; LUCAS, THAIS F. G.; PORTO, CATARINA S.. Estrogen receptor beta (ER beta) mediates expression of beta-catenin and proliferation in prostate cancer cell line PC-3. Molecular and Cellular Endocrinology, v. 430, n. C, p. 12-24, JUL 15 2016. (08/56564-1, 14/05292-2)

CAVALCANTI, FERNANDA N.; LUCAS, THAIS F. G.; LAZARI, MARIA FATIMA M.; PORTO, CATARINA S.. Estrogen receptor ESR1 mediates activation of ERK1/2, CREB, and ELK1 in the corpus of the epididymis. JOURNAL OF MOLECULAR ENDOCRINOLOGY, v. 54, n. 3, p. 339-349, JUN 2015. (08/56564-1)

PISOLATO, R.; LOMBARDI, A. P. G.; VICENTE, C. M.; LUCAS, T. F. G.; LAZARI, M. F. M.; PORTO, C. S.. Expression and regulation of the estrogen receptors in PC-3 human prostate cancer cells. Steroids, v. 107, p. 74-86, MAR 2016. (08/56564-1)