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Impact of Estrogen on Uterine Glucose Metabolism

Impact of Estrogen on Uterine Glucose Metabolism. Caitlin Murphy Dr. Fred Stormshak Department of Animal Science. Relevance. Human Impact Estrogens and xenoestrogens (endocrine disruptors) can promote uterine and breast cancer Animal Production

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Impact of Estrogen on Uterine Glucose Metabolism

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  1. Impact of Estrogen on Uterine Glucose Metabolism Caitlin Murphy Dr. Fred Stormshak Department of Animal Science

  2. Relevance • Human Impact • Estrogens and xenoestrogens (endocrine disruptors) can promote uterine and breast cancer • Animal Production • Better understanding of the mechanism of action of estrogens in regulation of reproductive cycles of livestock

  3. Background- Estradiol • Estradiol (E2) and progesterone (P4) are two of the major reproductive or “sex” hormones present in females. • The ovary is the major production site • Through appropriately timed production of both hormones during the estrous or menstrual cycle, ovulation is stimulated

  4. Responses of Target Cells to Estrogens • Short term (1-6 hours after exposure) • Increases hyperemia • Increases imbibition of water • Increases glucose oxidation and lipid synthesis • Increases RNA polymerase activity • Long term (6-48 hours after exposure) • Continued stimulation of RNA polymerase activity • Increases DNA synthesis • Increases in cell hypertrophy and hyperplasia

  5. Background-Glucose Oxidation • When glucose is oxidized, energy is derived through the process of glycolysis and the Krebs cycle 6O2 + C6H12O6→ 6CO2 + 6H2O + ATP(energy)

  6. Previous observations • Estradiol (E2) stimulated an increase in the metabolism of glucose to CO2 in rat uteri (Stormshak et al) • Increase in Glucose-6-Phosphate Dehydrogenase due to estrogen stimulation (Barker et al)

  7. Previous Observations- continued Glucose *Glucose Transporter GT-Glucose hexokinase Glycolysis G-6-P *Glucose-6-phosphate dehydrogenase *Been shown to be stimulated by estrogen Pentose phosphate pathway

  8. Hypothesis tested • Does estradiol (E2) stimulate nuclear-induced signaling of glucose oxidation in the ovine endometrium?

  9. 10 day treatment schedule of ovariectomized ewes

  10. Removal of endometrial tissue during surgery • Tissue is removed from the endometrium of left and right uterine horns • Tissue was kept at 4° C for transport to the laboratory and until processed • Once tissue is collected 3 assays were done to determine- • glucose oxidation • presence of nuclear estrogen receptors • amount of DNA Endometrium

  11. Experiment # 1- DNA assay • Estradiol causes imbibition of water into cells • Results for both the amount of estrogen receptors and glucose metabolism are expressed as per µg of DNA Control E2 treated H2O H2O H2O H2O H2O

  12. Results- DNA Assay *P< 0.05 DNA (µg)/ (mg) tissue

  13. Experiment #2- Nuclear Estrogen Receptors • A radioreceptor exchange assay was used to determine the effect of treatments on the concentration of nuclear estrogen receptors • Stimulated in treatment animals • Low stimulation for control animals

  14. Methods- nuclear estrogen receptors • Tissue was homogenized and the nuclear pellet was isolated • To determine specific binding of [3H]-estradiol the nuclear pellet was treated with either • 2 x 10-8 M [3H]-estradiol (for total binding) • 2 x 10-8 M [3H]-estradiol and 2 x 10-6 M diethylstilbestrol (for non-specific binding) • SB= total - NSB • Nuclear pellet was then incubated at 37º C, cooled and placed in EtOH overnight • EtOH was then measured in scintillation counter to determine concentration of [3H]-estradiol

  15. Results- Nuclear Estrogen Receptors *P< 0.05 E2 bound (fmol)/DNA (µg)

  16. Experiment #3-Glucose Oxidation • Glucose oxidation was assayed to determined if E2 would cause endometrial tissue to take in glucose and metabolize it • through glycolysis and the Krebs cycle • Ultimately produce CO2 and energy

  17. Methods-Glucose Oxidation

  18. Results- Glucose Oxidation *P< 0.05 14 CO2(cpm)/DNA (µg)

  19. Conclusion • Estrogen stimulates a nuclear-induced signal to cause the metabolism of glucose to CO2 in the ovine endometrium Glucose E2 E2 Energy Nucleus CO2

  20. Acknowledgements • Howard Hughes Medical Institute (HHMI) • Undergraduate Research Innovation Scholarship and Creativity (URISC) • Dr. Fred Stormshak • Reed Reeve • Tari Tan • Jared Deitz • Cecily Bishop

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