Corticosteroid synthesis in the human adrenal cortex requires a supply of
cholesterol which can be derived from both local synthesis and the uptake of plasma
lipoproteins. Studies with cultured adrenal cells have shown that such uptake is mediated through the interaction of plasma
low density lipoproteins (
LDL) and a specific cellular receptor (the
LDL receptor). In the present study we have examined parameters of adrenal
corticosteroid production in a patient with phenotypic
abetalipoproteinemia (on the basis of homozygous
hypobetalipoproteinemia) and in three of her relatives with inherently low levels of
LDL (heterozygous
hypobetalipoproteinemia). These studies sought to determine whether the absence of
LDL or an inherent reduction in their plasma concentration results in alterations in
corticosteroid production both under basal conditions and in response to prolonged stimulation with iv
ACTH. Our results document normal parameters of
corticosteroid production under basal conditions in both heterozygous and homozygous
hypobetalipoproteinemia, but an impaired response to
ACTH in the latter. This was manifested by significantly lower serum concentrations of
cortisol as well as by reduced rates of excretion of 17OHCS,
17-ketosteroids, and urinary free
cortisol during
ACTH infusion. By inference, our results provide in vivo support for the view that plasma
LDL serve as an important source of
cholesterol for adrenal
corticosteroid synthesis under conditions of sustained stimulation with
ACTH.