DEVELOPMENTALLY-REGULATED EXPRESSION OF ADRENAL 17-ALPHA-HYDROXYLASE CYTOCHROME-P450 IN THE MOUSE EMBRYO

Corticosterone is the major circulating glucocorticoid in adult mice a nd rats, and this is explained, in part, by the absence of 17 alpha-hy droxylase cytochrome P450 (P450c17) in adrenal glands of these rodents . During embryonic development, however, we discovered transient expre ssion of P450c17 in a subset of adrenocortical cells in the fetal mous e adrenal. This differs from cholesterol side-chain cleavage cytochrom e P450 and adrenodoxin, which are expressed continuously in most fetal adrenocortical cells from onset-of expression at embryonic days 11-12 (E11-12) until term. Adrenal P450c17 transcripts are detectable in, s itu at E12.5 and increase in abundance from E12.5 to E14.5. Transcript s are then lost between E16.5 and term (E18.5) and are undetectable in situ in adrenal glands of adult mice. These results are consistent wi th the presence of pregnenolone 17 alpha-hydroxylase activity in adren al homogenates of fetal but not adult mice. By using polymerase chain reaction, we determined that murine fetal (E14.5-15.5) adrenal glands contain messenger RNAs (mRNAs) encoding all of the steroid hydroxylase s required to produce cortisol and corticosterone but little aldostero ne synthase mRNA. Adrenal glands from adult mice contain mRNAs encodin g steroid hydroxylases required to produce corticosterone and aldoster one but not cortisol (little P450c17 mRNA). The spatial and temporal e xpression patterns of P450c17 and aldosterone synthase mRNA, which dif fer from those of cholesterol side-chain cleavage cytochrome P450 and adrenodoxin, suggest that multiple factors must be required to program cell type- and species-specific expression of these steroid hydroxyla ses during embryonic development.