Adrenal medullary cells in adult primates contain catecholamines and several 
neuropeptides. Among these peptides are several products of the three opiate 
precursor proteins: proenkephalin, prodynorphin, and proopiomelanocortin. We 
used immunocytochemistry to study the ontogeny of leu-enkephalin and the 
catecholamine-synthesizing enzymes dopamine beta-hydroxylase and 
phenylethanolamine N-methyltransferase in adjacent sections of 14 fetal rhesus 
and 31 fetal human adrenal glands. The adrenal medulla of a 24-week-old human 
fetus as well as medullas of 11 134- to 172-day-old rhesus fetuses were 
immunopositive with all 3 antisera employed. Furthermore, in thin serial 
sections of these glands, dopamine beta-hydroxylase, phenylethanolamine 
N-methyltransferase, and leu-enkephalin appeared to be colocalized in the same 
cells of the adrenal medulla. Twenty-six adrenals from fetuses 15-26 weeks 
stained lightly with one or more of the antisera. Dopamine beta-hydroxylase 
could be detected at 15 weeks, followed by leu-enkephalin and phenylethanolamine 
N-methyltransferase at 18-19 weeks. The role of the enkephalins during fetal 
life or in the adaptation to extrauterine life is not yet clear. In adults, 
enkephalins are cosecreted with catecholamines in response to stress. Our 
results suggest that the fetal adrenal may be capable of cosecretion of 
catecholamines and enkephalins, at least by the end of the second trimester of 
gestation.