Estradiol stimulates protein, RNA, and ultimately DNA synthesis in the uterus. The earliest uterine responses seen after estrogen administration occur within minutes. Some of these responses are incorporation of labelled uridine into RNA, histone acetylation, eosinophil infiltration into the uterus, synthesis of mRNA for induced protein, RNA polymerase activity, a decrease in arginine-rich histone content, an increase in glucose uptake, and an increase in amino acid uptake. Among later uterine responses to estrogen requiring 6 hours or more are generalized protein synthesis, and the increase in the activity of the hexose monophosphate shunt enzymes.
The classical model of induction of the response of the uterus to estradiol is the two-site model proposed by Gorski et al. (11) and Jensen et al. (12). This model is based on studies of the binding of radioactive estradiol to receptor in various cell fractions. According to this model, estradiol enters the cytoplasm and binds to the receptor. The receptor upon estradiol binding has a sedimentation coefficent which changes from 4S to 5S and is then translocated to the nucleus. Once in the nucleus, the receptor-estradiol complex binds to chromatin. It is through this interaction that estradiol induces changes in cellular activity. This model, however, is inconsistent with the findings of Welshons et al. who showed that cytoplasts (cells enucleated with cytochalasin B) showed little estrogen binding activity while the nucleoplasts showed considerable estrogen binding activity. In addition, the studies of King and Greene, using a monoclonal antibody against the estrogen receptor and immunochemical staining, showed that specific staining was confined to the nucleus. These last two studies support the conclusion that the estradiol receptor resides in the nucleus and not in the cytoplasm and that the cytoplasmic receptor may be an artifact of the fractionation procedures.
Jensen and Jacobsen in 1962 showed that the uterus and vagina of rats injected with [3H]estradiol retained the label for six hours while other tissues such and kidney and blood had increased levels of hormone for approximately two hours after administration. This discovery suggested that a receptor molecule in these organs was specifically binding to estradiol. Noteboom and Gorski in 1965 quantitated an estrogen receptor and determined the dissociation constant (Kd) to be 0.7 nM. Estrogen binding was found to be localized in cytosol, nuclear, mitochondrial, and microsomal fractions. In 1979, Pietras and Szego reported the presence of an estrogen receptor on the plasma membrane. These results were supported by the work of Nenci et al. using fluoresent estrogen analogs. However, these results are in contrast to the findings of Mueller et al. who were unable to demonstrate the presence of an estrogen receptor on the plasma membrane.
CONTENTS
ACKNOWLEDGEMENTS
ABSTRACT
LIST OF TABLES
LIST OF FIGURES
1. INTRODUCTION
2. CHARACTERIZATION OF THE GLUCOSE TRANSPORTER
- Introduction
Materials and Methods
Results
Discussion
3. CHARACTERIZATION OF ESTRADIOL STIMULATION OF GLUCOSE TRANSPORT
- Introduction
Materials and Methods
Results
Discussion
4. GLUCOSE TRANSPORT AND ESTROGEN RECEPTORS
- Introduction
Materials and Methods
Results
Discussion
5. INSULIN AND GLUCOSE TRANSPORT
- Introduction
Materials and Methods
Results
Discussion
6. MECHANISM OF THE ESTRADIOL-MEDIATED INCREASE IN GLUCOSE TRANSPORT
- Introduction
Materials and Methods
Results
Discussion
7. SUMMARY
REFERENCES
Download
PDF Ebook Estradiol Stimulation Of Glucose Transport In Rat Uterus
