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Progesterone and estrogen regulate NALCN expression in human myometrial smooth muscle cells.

07:00 EST 14th January 2020 | BioPortfolio

Summary of "Progesterone and estrogen regulate NALCN expression in human myometrial smooth muscle cells."

During pregnancy, the uterus transitions from a quiescent state to an excitable, highly contractile state to deliver the fetus. Two important contributors essential for this transition are hormones and ion channels, both of which modulate myometrial smooth muscle cell (MSMC) excitability. Recently, the Na leak channel, non-selective (NALCN) was shown to contribute to a Na leak current in human MSMCs, and mice lacking NALCN in the uterus had dysfunctional labor. Microarray data suggested that the pro-quiescent hormone progesterone (P4) and the pro-contractile hormone estrogen (E2) regulated this channel. Here, we sought to determine whether P4 and E2 directly regulate NALCN. In human MSMCs, we found that NALCN mRNA expression decreased by 2.3-fold in the presence of E2 and increased by 5.6-fold in the presence of P4. Similarly, E2 treatment decreased, and P4 treatment restored, NALCN protein expression. Additionally, E2 significantly inhibited and P4 significantly enhanced an NALCN-dependent leak current in MSMCs. Finally, we identified estrogen response and progesterone response elements (ERE and PRE) in the NALCN promoter. Using luciferase assays, we showed that the PREs, but not the ERE, contributed to regulation of NALCN expression. Our findings reveal a new mechanism by which NALCN is regulated in the myometrium and suggest a novel role for NALCN in pregnancy.

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This article was published in the following journal.

Name: American journal of physiology. Endocrinology and metabolism
ISSN: 1522-1555
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