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Cell and Molecular Biology of the Uterus

Volume 230 of the series Advances in Experimental Medicine and Biology pp 49-78

Progesterone-Modulation of Estrogen Action: Rapid Down Regulation of Nuclear Acceptor Sites for the Estrogen Receptor

  • Wendell W. LeavittAffiliated withDepartment of Biochemistry, Texas Tech University Health Sciences Center
  • , Andrea D. CobbAffiliated withDepartment of Biochemistry, Texas Tech University Health Sciences Center
  • , Akihiro TakedaAffiliated withDepartment of Biochemistry, Texas Tech University Health Sciences Center

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Summary

Our previous studies demonstrated that progesterone down regulates the occupied form of nuclear estrogen receptor (Re). Using the density shift method, we discovered that progestins stimulate the turnover of nuclear Re within 3 h of treatment, and Re synthesis is suppressed subsequently. Thus, the primary site of progestin action in down-regulating Re is the stimulation of nuclear Re turnover followed by the inhibition of Re replenishment. A major breakthrough in our understanding of how progestin controls Re turnover was made by studying nuclear acceptor sites for Re that were found to decrease markedly within 2 h of progestin treatment. These and other results indicate that progestin induces a factor called the Re regulatory factor (ReRF) which acts to block nuclear Re acceptor sites, and this in turn decreases nuclear Re retention on chromatin acceptor sites, leading to an enhanced turnover (or processing) of nuclear Re.