Comprehensive Physiology Wiley Online Library

Steroid Hormone Receptor Families

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Molecular Composition of Receptor Proteins: Primary Structural Homologies and Functional Domains
1.1 The A/B Region of Steroid Receptors Contains a Hormone‐Independent Activation Function
1.2 The C Region Encodes a Specific DNA‐Binding Function
1.3 The D Region (the Hinge Domain) Contains a Nuclear Localization Signal
2 The E/F Region Contains the Hormone‐Binding Domain, a Dimerization Motif, Steroid Receptor Repressor Activity, and a Receptor Agonist‐Dependent Transcriptional Activation Function
3 Receptor‐Associated Proteins and the Oligomeric Structure of Steroid Receptors
3.1 Major Heat Shock Proteins
4 Cross‐Talk with Other Signal‐Transduction Pathways
4.1 Cyclic Adenosine Monophosphate and Activation of Steroid Receptors
4.2 Transcriptional Interference
4.3 Pathways That Converge on the Estrogen Receptor
5 Role of Phosphorylation in Steroid Receptor Structure and Function
5.1 Sites of Phosphorylation, Functional Significance, and Regulatory Kinases
5.2 Estrogen Receptor Phosphorylation
5.3 Progesterone Receptor Phosphorylation
5.4 Glucocorticoid Receptor Phosphorylation
5.5 Vitamin D Receptor Phosphorylation
6 Transactivation by Steroid Receptors
7 Antihormones and Their Modes of Action
7.1 RU486, an Agonist/Antagonist of Progesterone Receptor
7.2 ZK98299, a Full Antagonist of Progesterone Receptor
7.3 Antiestrogens and Estrogen Receptor Function
8 Steroid Receptors and Clinical Management of Cancer
8.1 Cancer: Molecular Aspects
8.2 Breast Cancer, Tumor Suppressors, and Estrogen
8.3 Paradoxical Effects of Estrogen: Molecular Aspects
9 Future Directions
Figure 1. Figure 1.

Primary domain structure of human estrogen receptor. Illustrated are regions A–F with subdomins and their functions represented as block lines. Also shown are the kinases that phosphorylate human estrogen receptor and their sites of action. MAPK, mitogen‐activated protein kinase; CKII, casein kinase II; Src, tyrosine‐specific kinase protooncogene originally isolated as the Rous sarcoma (Src) virus oncogene; HSP, heat shock protein; AF, activation function.

Figure 2. Figure 2.

Linkage of estrogen and antiestrogen action to the tumor suppressors, retinoblastoma protein (pRB), and p53. 1, Increase in the levels/activity of p53 induced by 17β‐estradiol (E2); 2, wild‐type p53 induction of cell‐cycle inhibitors and apoptosis; 3, antiestrogen ICI 182,780 causes down‐regulation of cyclin D1, a decrease in the activity of cyclin D1‐associated Cdk2 activity, and dephosphorylation of pRB; 4, dephosphorylated pRB represses E2F, a transcription factor that induces G1 to S phase transition. Cells arrested at G1 phase of the cell cycle. Cdk, cylin‐dependent kinase; p53, protein product of the p53 gene.

Figure 3. Figure 3.

Effect of charcoal treatment on p53 levels in T47D cells: Western analysis. T47D cells were plated in whole serum for 2 days. Cells were then cultured for various times in medium containing whole (C) or charcoal‐treated serum (3–8 days). All cells were harvested at the same time after 10 days of culturing. Cells were extracted and analyzed for protein, and a total of 100 μg of protein/lane was applied for SDS‐PAGE and Western blot analyses as described . [Taken with permission from the American Society for Biochemistry and Molecular Biology for the article J. Biol. Chem. 270: 28507–28510, 1995.]

Figure 4. Figure 4.

Effect of estradiol concentrations on p53 levels in T47D cells cultured in charcoal‐treated serum: Western blot analysis. T47D cells were plated for 2 days in medium containing whole serum and then for another 6 days in charcoal‐treated serum plus estradiol as indicated. Lane C represents cells cultured in whole serum for the entire time with no exogenous estradiol treatment. Lane 0 represents a sample with charcoal treatment but no estradiol addition (control). All cells were harvested at the same time after 8 days of culturing. Procedures for SDS‐PAGE and Western blot analyses were the same as those used for the experiment described in Figure and detailed in reference . [Taken with permission from the American Society for Biochemistry and Molecular Biology for the article J. Biol. Chem. 270: 28507–28510, 1995.]



Figure 1.

Primary domain structure of human estrogen receptor. Illustrated are regions A–F with subdomins and their functions represented as block lines. Also shown are the kinases that phosphorylate human estrogen receptor and their sites of action. MAPK, mitogen‐activated protein kinase; CKII, casein kinase II; Src, tyrosine‐specific kinase protooncogene originally isolated as the Rous sarcoma (Src) virus oncogene; HSP, heat shock protein; AF, activation function.



Figure 2.

Linkage of estrogen and antiestrogen action to the tumor suppressors, retinoblastoma protein (pRB), and p53. 1, Increase in the levels/activity of p53 induced by 17β‐estradiol (E2); 2, wild‐type p53 induction of cell‐cycle inhibitors and apoptosis; 3, antiestrogen ICI 182,780 causes down‐regulation of cyclin D1, a decrease in the activity of cyclin D1‐associated Cdk2 activity, and dephosphorylation of pRB; 4, dephosphorylated pRB represses E2F, a transcription factor that induces G1 to S phase transition. Cells arrested at G1 phase of the cell cycle. Cdk, cylin‐dependent kinase; p53, protein product of the p53 gene.



Figure 3.

Effect of charcoal treatment on p53 levels in T47D cells: Western analysis. T47D cells were plated in whole serum for 2 days. Cells were then cultured for various times in medium containing whole (C) or charcoal‐treated serum (3–8 days). All cells were harvested at the same time after 10 days of culturing. Cells were extracted and analyzed for protein, and a total of 100 μg of protein/lane was applied for SDS‐PAGE and Western blot analyses as described . [Taken with permission from the American Society for Biochemistry and Molecular Biology for the article J. Biol. Chem. 270: 28507–28510, 1995.]



Figure 4.

Effect of estradiol concentrations on p53 levels in T47D cells cultured in charcoal‐treated serum: Western blot analysis. T47D cells were plated for 2 days in medium containing whole serum and then for another 6 days in charcoal‐treated serum plus estradiol as indicated. Lane C represents cells cultured in whole serum for the entire time with no exogenous estradiol treatment. Lane 0 represents a sample with charcoal treatment but no estradiol addition (control). All cells were harvested at the same time after 8 days of culturing. Procedures for SDS‐PAGE and Western blot analyses were the same as those used for the experiment described in Figure and detailed in reference . [Taken with permission from the American Society for Biochemistry and Molecular Biology for the article J. Biol. Chem. 270: 28507–28510, 1995.]

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Cliff Hurd, V. K. Moudgil. Steroid Hormone Receptor Families. Compr Physiol 2011, Supplement 20: Handbook of Physiology, The Endocrine System, Cellular Endocrinology: 383-411. First published in print 1998. doi: 10.1002/cphy.cp070115