A null mutation in the murine gene encoding steroid 5α-reductase type 1 (5αR1) leads to failure of normal parturition at term. This observation, together with the finding that mRNA levels of uterine 5αR1 increase significantly at term in normal pregnant animals, indicates that 5αR1 plays an important role in murine parturition. The current studies were conducted to elucidate the regulation of 5αR1 in uterine tissues of nonpregnant and pregnant animals. Nonpregnant, ovariectomized ICR mice were treated with vehicle (control), 17β-estradiol (E2), progesterone (P4 ), or E2 P4 for 3 days. Thereafter, uterine tissues were obtained for histology, quantification of 5αR1 specific activity, and Northern blot analysis of 5αR1 mRNA expression. The 5αR1 enzyme activity was significantly increased in animals treated with E2 P4. However, activity was much less in uterine tissues from E2 P4-treated animals than in uterine tissues from pregnant animals near term. To evaluate further the regulation of 5αR1 during gestation, mice underwent unilateral tubal ligation before timed matings. The 5αR1 activity increased eightfold in uterine tissues from the fetal horn from Gestational Days 12 to 18. This temporal pattern in 5αR1 activity paralleled marked increases in uterine diameter. Taken together, these studies indicate that expression of 5αR1 is regulated by E2 P4 in uterine tissues. Whereas E2 alone is insufficient to induce enzyme activity, E2 may be required to increase P4 receptors and, thereby, mediate the effects of P4 on 5αR1 gene expression. Further increases in enzyme activity during late gestation are mediated by fetal occupancy, possibly through stretch-induced increases in endometrial growth. Thus, like other genes involved in parturition, expression of 5αR1 is regulated by both hormonal and fetal-derived signaling pathways.
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