LOCALIZATION OF CYTOCHROME-P450 CHOLESTEROL SIDE-CHAIN CLEAVAGE, CYTOCHROME-P450 17-ALPHA-HYDROXYLASE 17,20-LYASE, AND 3-BETA-HYDROXYSTEROID DEHYDROGENASE ISOMERASE STEROIDOGENIC ENZYMES IN HUMAN AND RHESUS-MONKEY FETAL ADRENAL-GLANDS - REAPPRAISAL OF FUNCTIONAL ZONATION/

We examined the in situ localization of key steroidogenic enzymes in a drenal gland sections from midgestation (17-24 weeks) human fetuses an d late gestation (130-142 days; term = 165 days) rhesus monkey fetuses . The rhesus monkey fetal adrenals were used as a model for the late g estation human fetal adrenal. The enzymes examined were cytochrome P45 0 cholesterol side-chain cleavage (P450scc), cytochrome P450 17 alpha- hydroxylase/17,20-lyase (P450c17), and 3 beta-hydroxysteroid dehydroge nase/isomerase (3 beta HSD). In human fetal adrenals, P450scc and P450 c17 proteins and mRNAs were detected only in fetal zone (innermost cor tical zone) and transitional zone (between the fetal and definitive zo ne) cells, not in definitive zone cells. Expression of 3 beta HSD was not detected in any cortical zone cells in midgestation human fetal ad renals. In rhesus monkey fetal adrenals, a similar pattern of P450scc and P450c17 expression was observed in the fetal and transitional zone s. In the definitive zone cells of rhesus monkey fetal adrenals, expre ssion of both P450scc and 3 beta HSD was detected. In addition, low le vels of 3 beta HSD expression could be detected in some transitional z one cells. P450c17 expression was lacking in definitive zone cells fro m rhesus monkey fetal adrenals. These data suggest that early in gesta tion, cortisol is not produced by the human fetal adrenal cortex in vi vo (because it does not express 3 beta HSD), whereas androgen producti on occurs in the transitional and fetal zones (which express P450scc a nd P450c17). Later in gestation, the definitive zone may produce miner alocorticoids (because it expresses P450scc and 3 beta HSD, but lacks P450c17), and the transitional zone may produce glucocorticoids (it ex presses P450scc, P450c17, and 3 beta HSD), whereas the fetal zone cont inues to produce androgens. Thus, late in gestation the functional zon ation of the human fetal adrenal cortex may be similar to that of the adult, with the definitive zone being analogous to the nascent zona gl omerulosa, the transitional zone analogous to the zona fasciculata, an d the fetal zone analogous to the zona reticularis.