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It has been established that estrogen can alter circadian rhythms in behavior and endocrine physiology in rodents. The uterus is a reproductive organ that is critically dependent on regulation by ovarian steroids. Here, we examined the expression of  Per1  in different compartments of the uterus, and explored whether the ovarian steroids could regulate  Per1  expression employing ovariectomized rat uterus. RT-PCR analysis showed that  Per1  was cyclically expressed in the uterus. As revealed by  in situ  hybridization, the staining intensity of  Per1  mRNA was stronger at ZT 8 than at ZT 0 in the uterine luminal epithelium (LE), stroma (S), and myometrium (M) compartments, but was not changed in the glandular epithelium (GE). Both  in situ  hybridization and immunofluorescence analyses revealed that estradiol (E 2 ) administration induced high expression of  Per1  in the LE, GE, and M, and less expression in the S compartment. Progesterone (P 4 ) treatment resulted in an obvious enhancement of  Per1  expression in the LE, GE, and S, but unchanged in the M compartment. Furthermore, the E 2 - and P 4 -activated  Per1  expression was significantly repressed by their respective antagonists, ICI182 780 and RU486. These findings were further supported by RT-PCR analysis of  Per1  expression in cultured uterine stromal cells. Collectively, the present data indicate that E 2  and P 4  might be involved in modification of circadian rhythm via direct regulation of the expression of clock genes.

Up-regulation of Per1 expression by estradiol and progesterone in the rat uterus