Lipid synthesis in fetal skin may be important both for the developmen
t of a mature epidermal permeability barrier and for growth. In these
studies, we measured cutaneous cholesterol, sphingolipid and fatty aci
d synthesis during the critical period of epidermal barrier developmen
t in fetal rats to determine whether barrier function influences synth
etic rates. In addition, the activities of HMG CoA reductase, serine p
almitoyl transferase and acetyl coenzyme A carboxylase were evaluated.
In whole skin, synthesis of cholesterol, ceramide, sphingomyelin and
fatty acid decreased from day 17 to day 21 of gestation, as did the ac
tivity of HMG CoA reductase, serine palmitoyl transferase and acetyl c
oenzyme A carboxylase. In both the epidermis and dermis, a decrease in
cholesterol, ceramide, sphingomyelin and fatty acid synthesis was mea
sured over days 19-21 of gestation. Epidermal HMG CoA reductase activi
ty also decreased over this same time period. In summary, epidermal an
d dermal synthetic rates and enzyme activity were highest early in ges
tation when the barrier was least competent and decreased as competenc
e was achieved. Since other studies with mature animals have revealed
that epidermal synthetic rates and enzyme activity are highest when ba
rrier disruption is maximal, enhanced epidermal lipid synthesis preced
es the establishment of a competent barrier in both fetal and mature r
odents.