Estrogen-Modulated Uterine Gene Transcription in Relation to Decidualization*

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Abstract
Three daily injections of 2 mg progesterone are required to sensitize the uterus of the ovariectomized rat to deciduogenic stimuli. The period of uterine sensitivity is terminated by 17β-estradiol (E2). The mechanisms of sensitization and desensitization have been studied. The availability of DNA sequences in uterine chromatin for RNA chain initiation was assayed under conditions which eliminate chain elongation and reinitiations. A 500% increase in RNA initiation sites was stimulated and maintained by progesterone; this increase was closely correlated with the sensitivity of the uterus to decidualization. At anytime after three daily injections of 2 mg progesterone, the injection of E2 (0.2 μg) depressed the transcriptive activity of uterine chromatin below control levels within 4 h, but the uterus remained fully sensitive for 30 h. Desensitization then proceeded rapidly and was complete 40 h after E2. This refractive state (restricted transcription and absence of uterine sensitivity) persisted if injection of progesterone was continued. Progesterone withdrawal also desensitized the uterus and caused a depression in uterine chromatin transcription. The chronology of these events was different (restricted transcription and loss of uterine sensitivity occur simultaneously 28–36 h after the last progesterone injection) and suggested that E2 intervention and progesterone withdrawal operate by different mechanisms to desensitize the uterus. We suggest that E2 modulates progesterone-induced uterine sensitivity, primarily by the qualitative restriction of gene expression. The products of E2-altered transcription may regulate the transformation of a sensitive uterus to one receptive to the blastocyst and thus allow implantation before the loss of uterine sensitivity takes place.