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

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)