Plasma membrane sodium/calcium exchangers are an important component of intracellular calcium homeostasis and electrical conduction. NCKX3 (gene SLC24A3), a potassium-dependent sodium-/calcium exchanger, plays a critical role in the transport of one intracellular calcium and potassium ion across the cell membrane in exchange for four extracellular sodium ions. NCKX3 transcripts are most abundant in the brain and smooth muscle, but many other tissues, in particular, the uterus, aorta and intestine, also express this gene at lower levels. However, the expression and physiological roles of NCKX3 in the uterus of rats during the estrous cycle are unknown. Thus, we examined the uterine expression of NCKX3 mRNA and protein at different stages of the estrous cycle in mature and immature female rats in the absence or presence of the sex-steroid hormones estrogen (E2) and progesterone (P4). During the estrous cycle, uterine expression of NCKX3 mRNA and protein was enhanced up to 4.0- and 2.5-fold, respectively, at proestrus compared to during estrus and diestrus. To examine the effect of sex steroids on NCKX3 regulation in the uterus, immature female rats were treated with E2 (40 µg/kg body weight; BW), P4 (4 mg/kg BW), or E2 plus P4 for 3 days. The expression of NCKX3 mRNA and protein was induced by E2, whereas P4 antagonized E2-induced NCKX3 expression. Subsequent immunohistochemical analysis revealed that uterine NCKX3 protein was abundantly localized in the cytoplasm of luminal and glandular epithelial cells throughout the estrous cycle. Taken together, these results indicate that uterine NCKX3 is abundantly expressed in the uterus and that its expression is regulated by the steroid hormones, E2 and P4. These findings suggest that NCKX3 may be involved in reproductive function during the estrous cycle in female rats.
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