Introduction: E2 induces a biaphasic early (4 h) and late (24 h) increase in transcriptional activity of isolated uterine nucleoli. It is proposed that the early response of the uterus to E2 is to stimulate the elongation of nucleolar RNA synthesis and results from the synthesis of a short lived protein(s). One possible candidate for the E2 induced protein is ornithine decarboxylase. It is proposed that the longer termed response of the uterus to E2 for activation of nucleolar RNA synthesis is by increasing the rate of initiation of nucleolar RNA chains. This later response to E2 appears to result from alteration of uterine metabolism which results in a change in the glutathione status of the cell. It is further proposed that the glutathione status of the cell is important in activation/deactivation of nucleolar E2 binding sites which are located within the """"""""nculeolar or nuclear matrix."""""""" The aims of this proposal are directed towards determining the mechanisms by which E2 induces nucleolar RNA synthesis during the early and late phases of E2 action.
Specific Aims : 1) Determine the site of action of E2 on nucleolar RNA synthesis during the early (4 h) and late (24 h) response of the uterus to hormone administration by determining the number and the rate of elongation of RNA chains in isolated uterine nucleoli. 2) Determine the effect of in vivo administration of E2 on the protein composition of uterine nucleoli by determining whether E2 induces the synthesis of specific uterine nucleolar proteins and/or the modification (phosphorylation, acetylation, methylation) of nucleolar proteins. 3) Determine the role of ornithine decarboxylase in early and late E2 stimulation of uterine nucleolar RNA synthesis; and 4) Determine the mechanism by which in vivo administration of E2 (4 h and 24 h) activates the nucleolar estradiol binding sites by determining the GSH/GSSG levels in uterine cytosol, nuclei and nucleoli; determining the quantity of mixed disulfides present in uterine nucleoli, and determining whether glutathione is associated with the nucleolar E2 binding sites and the relation of the nucleolar E2 binding sites to the nuclear matrix and the nuclear matrix proteins.
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| Whelly, S M (1986) Estradiol regulation of uterine nucleolar estradiol binding sites. Biochim Biophys Acta 880:179-88 |
