Alternative splicing of Slo channel gene programmed by estrogen, progesterone and pregnancy

STREX alternative-exon adds to Slo channel a phosphorylation sequence that can invert protein kinase A (PKA) regulation from excitatory to inhibitory. Because pregnancy switches Slo responsiveness to PKA from inhibitory to excitatory, we hypothesized that STREX expression diminishes with pregnancy and is regulated by sex hormones. Different from total-rSlo, which is elevated around mid-pregnancy and decreases at term, STREX transcripts progressively decreased with pregnancy near 80% at term. STREX downregulation was mimicked by estrogen, and opposed by estrogen-receptor antagonist ICI 182,780 or progesterone (Pg). The regulation of STREX splicing directed by estrogen and Pg provides a mechanism for Slo’s PKA-related phenotypic alteration with pregnancy.