Sodium/potassium/calcium exchanger 3 is regulated by the steroid hormones estrogen and progesterone in the uterus of mice during the estrous cycle

Plasma membrane sodium/calcium exchangers are an important component of intracellular calcium homeostasis and electrical conduction. A member of the family of potassium-dependent sodium/calcium exchangers, NCKX3 (SLC24A3) plays a critical role in the transport of an intracellular calcium and potassium ion in exchange for four extracellular sodium ions. NCKX3 mRNA transcripts are particularly abundant in brain and smooth muscle, but many other tissues, including uterus, aorta, and intestine, also express NCKX3, albeit at lower levels. In the present study, we examined uterine expression of NCKX3 at the mRNA and protein levels during the estrous cycle in mature female ICR mice in the absence or presence of the sex steroid hormones estrogen (E2) and progesterone (P4). During the estrous cycle in mice, uterine expression of NCKX3 mRNA and protein was elevated at estrus as compared to proestrus and diestrus. To determine the role of sex steroids in the regulation of NCKX3 expression in the uterus, mice were treated with E2 (40 microg/kg body weight), P4 (4 mg/kg body weight) or E2 plus P4 for 3 days. The levels of NCKX3 mRNA in the uterus of mice were significantly reduced by E2 or P4 treatment. Co-treatment with E2 and P4 caused a significant decrease in the transcription of NCKX3 as compared to E2 or P4 alone, but the effect was not synergistic. Using immunohistochemistry, we identified abundant levels of uterine NCKX3 in the cytoplasm of luminal and glandular epithelial cells at estrus. The results of the present study indicate that NCKX3 is abundantly expressed in the uterus and that its expression is regulated by the steroid hormones E2 and P4. Thus, uterine expression of NCKX3 might be involved in reproductive function during the estrous cycle in female mice.