Distinct Expression of the Calcium Exchangers,NCKX3 and NCX1,and Their Regulation by Steroid in the Human Endometrium During the Menstrual Cycle

Abstract

Plasma membrane sodium/calcium exchangers are an important component of intracellular calcium homeostasis and electrical conduction. The potassium-dependent sodium/calcium exchangers NCKX3 (gene SLC24A3) and NCX1 (gene SLC8A1) play a critical role in the transport of intracellular calcium across the cell membrane in exchange for extracellular sodium ions. NCKX3 and NCX1 transcripts are most abundant in the brain and smooth muscle, but many other tissues, particularly the uterus, aorta, and intestine, also express this gene at lower levels. However, the expression patterns and physiological roles of NCKX3 and NCX1 in the human endometrium during the menstrual cycle are unknown. Thus, we examined the endometrial expression of NCKX3 and NCX1 messenger RNA (mRNA) and protein throughout the different phases of the menstrual cycle. Endometrial expression of NCKX3 mRNA and protein was increased 1.5- to 2.5-fold during the early-proliferative, mid-proliferative, and early-secretory phases compared with the other phases; however, no significant alteration in NCX1 expression level was observed. The effects of the sex-steroid hormones, 17β-estradiol (E2) and progesterone (P4), on the expression of NCKX3 and NCX1 in Ishikawa cells was also investigated. NCKX3 expression was significantly increased by E2 (10⁻⁸ mol/L). However, the expression of NCX1 was not affected by E2 and P4. Subsequent immunohistochemical analysis revealed that the uterine NCKX3 and NCX1 proteins were abundantly localized in the cytoplasm of luminal and glandular epithelial cells throughout the menstrual cycle. Taken together, these results indicate that NCKX3 is abundantly expressed within the human endometrium at the transcriptional and translational levels, and its level appears to be regulated by a steroid hormone, in particular, E2 during the human menstrual cycle.