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Estrogen Receptor Activation by Ligand-Dependent and Ligand-Independent Pathways

  • Chapter
Steroid Hormone Receptors: Basic and Clinical Aspects

Part of the book series: Hormones in Health and Disease ((HHD))

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Abstract

Estrogens are a class of female sex steroid hormones important for the growth and differentiation of mammary and reproductive tissues and brain. The biological activities of these hormones are mediated by the estrogen receptor (ER), an intracellular phosphoprotein which binds a comparatively small molecular weight steroidal ligand and transduces its signal to the nuclear genetic apparatus. This protein belongs to a gene superfamily of ligand-activated transcription factors whose members are distinguished by the presence of three regions of homology, named C1, C2 and C3 (Carson-Jurica et al, 1990). The region of greatest conservation, C1, is composed of a sequence motif of 66-68 amino acids proposed to form two type II zinc fingers (Evans, 1988; Carson-Jurica et al, 1990; Green and Chambon, 1991 and references therein). Each finger contains 4 invariant cysteine residues thought to coordinate a single zinc atom and together these fingers in the context of the surrounding amino acid sequence determine the specificity of receptor binding to DNA (reviewed by Freedman, 1992). The characteristic homology of this region has been exploited to allow the rapid identification of new gene superfamily members in species as diverse as sea urchin (Chan et al, 1992), Drosophila (Mlodzik et al, 1990) and man (Wang et al, 1989), and although the final size of this superfamily is presently unknown, estimates suggest it may eventually encompass as many as 50 members (O’Malley and Conneely, 1992). Of the members identified to date, there are two major subgroups: those for which a ligand has been identified such as the steroidAhyroid/vitamin receptors, and those for which a putative ligand, if any, is currently unknown (O’Malley, 1990). These latter proteins, referred to as ‘orphan’ receptors, are the subject of ongoing investigations to determine their physiological ligand and/or other factors that may regulate their transcriptional activity.

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  1. Department of Cell Biology, Baylor College of Medicine, USA

    Carolyn L. Smith, Orla M. Conneely & Bert W. O’Malley

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  1. Carolyn L. Smith
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  1. Department of Biological Sciences, Oakland University, Rochester, Michigan, 48309-4401, USA

    V. K. Moudgil

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© 1994 Birkhäuser Boston

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Smith, C.L., Conneely, O.M., O’Malley, B.W. (1994). Estrogen Receptor Activation by Ligand-Dependent and Ligand-Independent Pathways. In: Moudgil, V.K. (eds) Steroid Hormone Receptors: Basic and Clinical Aspects. Hormones in Health and Disease. Birkhäuser Boston. https://doi.org/10.1007/978-1-4615-9849-7_13

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