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 Title: Estrogen Receptor and Progesterone Receptor Synthesis and Degradation in Target Cells Author(s): Nardulli, Ann Marie Department / Program: Physiology and Biophysics Discipline: Physiology Degree Granting Institution: University of Illinois at Urbana-Champaign Degree: Ph.D. Genre: Dissertation Subject(s): Biology, Animal Physiology Abstract: The rates of synthesis and degradation of steroid hormone receptors are crucial factors in maintaining hormone responsiveness in target tissues. It was the intent of this study to determine the turnover of the estrogen receptor (ER) and progesterone receptors (PR) in rat uterine and human breast cancer cells, respectively, and to examine the effect of estrogen and progestin on PR levels.The rates of synthesis and degradation of ER were determined in rat uterine cells in vitro and in vivo. The affinity labeling antiestrogen, ($\sp3$H) tamoxifen aziridine, was used in pulse chase experiments to show that the 65,000 molecular weight ER has a half-life of 3-4h in primary cultures of rat uterine cells in vitro and in the intact rat uterus in vivo. Density shift analyses using dense ($\sp$N, $\sp$C, $\sp2$H) amino acid incorporation corroborate the rapid turnover of ER in rat uterine cell cultures.The fact that PR content increases in response to estrogen treatment has long been known, but the mechanism by which this increase occurs has remained obscure. Dense amino acid-density shift analysis was utilized to determine how this increase in receptor level is mediated. When MCF-7 breast cancer cells are exposed to 6 $\times$ 10$\sp{-11}$ and 3 $\times$ 10$\sp{-11}$ M estradiol, PR rises to maximal and half maximal levels, respectively. The increased levels of PR protein are associated with increased levels of PR mRNA. Because receptor degradation is identical in cells maintaining maximal and half maximal PR levels, it is believed that the rise in PR content with estrogen exposure is due to increases in receptor synthesis.The regulation of PR by progestins in T47D human breast cancer cells was examined using density shift-dense amino acid incorporation. When T47D cells, which normally maintain high PR levels, are exposed to progestin (R5020), PR levels decline. Receptor half-life, which is 21h in control cells, is reduced to 6h when cells are exposed to 20 nM ($\sp3$H) R5020. In addition, PR synthesis rate declines exponentially following R5020 exposure. The reduction in receptor level is thus due to dramatic increases in PR degradation as well as marked decreases in PR synthesis. Issue Date: 1987 Type: Text Description: 146 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1987. URI: http://hdl.handle.net/2142/71454 Other Identifier(s): (UMI)AAI8803149 Date Available in IDEALS: 2014-12-16 Date Deposited: 1987
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