Developmental regulation of alternatively spliced acetyl-CoA carboxylase-α mRNAs encoding isozymes with or without an eight amino acid domain upstream of the Ser-1200 phosphorylation motif in the mammary gland

Abstract

Expression of a variant acetyl-CoA carboxylase-α (ACC-α) mRNA encoding an isozyme either comprising (+24nt) or lacking (Δ24nt) an eight amino acid domain proximal to the Ser-1200 phosphorylation motif has been investigated in ovine and rat mammary tissue throughout pregnancy and lactation. The ratio of the Δ24nt mRNA: +24nt mRNA in ovine tissues varied from 0.1-0.25 (spleen, lung, muscle, heart, adipose tissue, brain) to 0.6-0.8 (pancreas, liver, kidney) to approximately 5.0 (lactating mammary gland). The sixfold increase in total ACC-α mRNA expression in mammary gland during lactation was due entirely to a tenfold increase in the level of the Δ24nt species as the level of expression of the +24nt species remained unaltered between pregnancy and lactation. This mode of expression of the +24nt and Δ24nt mRNAs was similar in rat mammary gland. Between day 20 of pregnancy and day 4 of lactation the ratio of the Δ24nt:+24nt mRNA increased from 2:1 to 10-20:1. Forced involution reduced the ratio of the two mRNAs to levels observed throughout pregnancy. Treatment of lactating rats with bromocryptine reduced the ratio of the Δ24nt:+24nt mRNA to relative levels observed after forced involution, suggesting that the exonic splicing responsible for the generation of the two mRNA isoforms is prolactin responsive.