The characteristics of 3-hydroxy-3-methylglutaryl-CoA reductase from mouse uterine epithelial cells were studied. Preliminary experiments showed that enzyme activity was stimulated approx. 10-fold 18h after administration of 100ng of oestradiol-17 beta. This activity was associated with all particulate fractions of the uterine luminal cell. The Km for D-3-hydroxy-3-methylglutaryl-CoA was 5.54 +/- 1.12 microM. The detailed time-course of oestrogen stimulation showed two peaks of activity, 9 and 15h after hormone treatment. The DNA content of the epithelial cells doubled between 6 and 12h after hormone treatment, whereas the protein content increased linearly over the 18h period. The peak of enzyme activity at 9h is associated with early S phase of the epithelial cells; the peak at 15h may be associated with a second S phase or with mitosis. Pretreatment with progesterone for 3 days before injection of oestradiol-17 beta (a treatment which inhibits uterine epithelial DNA synthesis) reduced the oestrogenic stimulation of enzyme activity by 63%; progesterone treatment alone did not stimulate enzyme activity. These data suggest that uterine epithelial 3-hydroxy-3-methylglutaryl-CoA reductase may play an important role in the cell cycle in this tissue.

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