Regulation of Slo potassium channel alternative splicing in the pituitary by gonadal testosterone

Slo gene-encoded BK potassium channels are prominent in both adrenomedullary and pituitary tissues. At one alternative splicing site, both tissues express variants with and without the optional 'STREX' exon. In adrenal chromaffin cells, this splicing choice, which has important ramifications for cell excitability, has been shown to be regulated by steroid hormones, including glucocorticoids and adrenal androgens. Moreover, striking sex differences are seen between male and female tree shrews. Here, we test the hypothesis that gonadal testosterone regulates splicing in these tissues. No significant sex differences were found in rats, in either adrenals or pituitaries. In the adrenal medulla, prepubertal castration in male rats increased the relative abundance of STREX transcripts slightly, but not significantly, as measured several weeks after puberty. However, castration substantially decreased STREX representation in the rat pituitary. Silastic implants of testosterone inserted at castration prevented this STREX decline. In postpubescent males, castration or T implants had less effect. Thus, we report (i) steroidal regulation of Slo splicing in the pituitary and (ii) participation of the male gonads in this regulation.