201 SODIUM/POTASSIUM/CALCIUM EXCHANGER 3, NCKX3, IS REGULATED BY ESTROGEN AND PROGESTERONE IN THE UTERUS OF MICE DURING ESTROUS CYCLE

Abstract

As a member of family of potassium-dependent sodium/calcium exchangers, a sodium/potassium/calcium exchanger NCKX3 (slc24a3), plays a critical role in transport of 1 intracellular calcium and potassium ion in exchange for 4 extracellular sodium ions. Transcripts of NCKX3 were most abundant in the brain, but many other tissues have been shown to express NCKX3 at lower levels, especially uterus, aorta, and intestine, which are rich in smooth muscle. Thus, we further investigated uterine NCKX3 mRNA expression during the estrous cycle in the absence or presence of sex-steroid hormones estrogen (E2) and progesterone (P4) in mature (>14 wk old) female ICR mice (total n = 15). NCKX3 was expressed in the uterus of female reproductive system and regulated by E2 or P4. During estrous cycle of the mice, uterine NCKX3 mRNA level fluctuated, and its mRNA level was down-regulated when E2 and P4 levels were high (proestus and estrus), whereas its level disappeared at metestrus and diestrus. In addition, NCKX3 protein expression was identified in the uterus of mice by immunohistochemistry. To examine the roles of sex steroids, the mice were treated with E2 [40 μg kg^–1 body weight (BW)] or P4 (4 mg kg^–1 of BW) and E2 plus P4 for 3 days. The expression level of NCKX3 mRNA was significantly decreased by E2 or P4 in the uterus of mice. However, co-administration of E2 and P4 caused a significant decline at the transcriptional level of this gene when compared with vehicle or P4 treatment alone, suggesting an inhibition role of E2 in response to P4. Taken together, these results indicate that uterine NCKX3 expression is regulated during the estrous cycle, and its expression is mainly controlled by E2 and P4, suggesting that uterine NCKX3 in female mice may be involved in the function of female reproductive system.