Female reproductive organs are mainly regulated by estrogen and progesterone. Specifically, the uterus, vagina and mammary gland show organ-specific mitosis and morphological changes during proliferative events, such as estrous cycle, gestation and lactation. The mechanism underlying these organ-specific estrogen-dependent events is still unknown. We examined, therefore, global gene expression in the mature uterus, vagina and mammary gland of ovariectomized adult mice 6 hr after an injection of 5 μg/kg 17β-estradiol (E
2) using a microarray method in order to identify primary E
2-responsive genes. Half of the E
2 up-regulated genes in the uterus were similar to those in the vagina. E
2 up-regulated the expression of
Insulin-like growth factor 1 (Igf-1) genes in the uterus and vagina. In the vagina, E
2 up-regulated the expression of IGF binding proteins (
Igfbp2 and
Igfbp5). In the mammary gland, unlike the uterus and vagina, no gene showed altered expression 6 hr after the E
2 exposure. These results suggest that expression of
Igf-1 and morphogenesis genes is regulated by E
2 in an organ-specific manner, and it is supported by the results of BrdU labeling showing E
2-induced mitosis in the uterus and vagina except the mammary gland. The differences in organ specificity in response to E
2 may be attributed by differences in gene expression regulated by E
2 in female reproductive organs. The candidate estrogen-responsive genes in the uterus and vagina identified by profiling provide an important foundation understanding functional mechanisms of estrogen regulating morphogenesis and maintenance of each reproductive organ.
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