Developmental changes in renal renin mRNA half-life and responses to stimulation in fetal lambs

In the perinatal period there is increased renin gene expression in the kidney compared with other stages of development. This may be related to changes in responsiveness of the renin gene to stimulation and/or differences in renin mRNA stability as development progresses. To ascertain if either responsiveness or stability changes in fetal life, we studied renin mRNA levels in primary cultures of renal cortical cells obtained from fetal lamb kidneys at two stages (0.7 and 0.9) of gestation after stimulation with isoproterenol, forskolin, or isobutyl methylxanthine and after inhibition of transcription with actinomycin D. Forskolin and isobutyl methylxanthine rapidly increased renin mRNA by at least twofold in the cultured cells from fetuses of both ages, with the sensitivity to stimulation higher in the cells from the mature fetal kidneys. Isoproterenol was effective only in mature fetal cells. In addition, the decay of renin mRNA after cessation of transcription was slower in mature cells compared with immature cells, the half-life being 11.6 +/- 0.8 h in mature cells and 6.6 +/- 0.6 h in immature cells (P < 0.05). The data suggest that increases in both renin mRNA sensitivity to stimulation and in stability can contribute to the enhanced renin expression in the perinatal period.