Expression of low and high density lipoprotein receptor genes in human adrenals

Abstract

Corticosteroids are synthesized from cholesterol which may arise from de novo synthesis or from the uptake of low or high density lipoproteins (LDL or HDL). In the present study, we compared the expression and regulation patterns of LDL receptor and CLA-1 (CD36 and LIMPII Analogous-1, an HDL receptor) genes in adult human adrenocortical tissues to shed more light on the relative contribution of LDL and HDL in human adrenal steroidogenesis. By screening 64 normal and pathological adrenal samples by Northern blotting, we found a positive correlation between LDL receptor and CLA-1 mRNA expression in the adrenal tissues (r=0.547; spearman rank correlation test P<0.01). Adrenal tissues adjacent to Cushing's adenomas contained consistently less LDL receptor and CLA-1 mRNA than normal adrenals (Mann-Whitney P<0.05). In primary cultures of normal adrenal cells, accumulation of both LDL receptor and CLA-1 mRNAs was upregulated by ACTH in a dose- and time-dependent manner, with an earlier induction of LDL receptor than CLA-1 mRNA expression. (Bu)(2)cAMP also increased the levels of these two mRNAs. Addition of LDL, but not HDL, into the culture medium increased cortisol production in untreated adrenocortical cells. Both LDL and HDL enhanced ACTH-induced cortisol production, with the effect of LDL much stronger than that of HDL. Our data show that LDL receptor and CLA-1's expression is ACTH-dependent and occurs in parallel in human adrenal tissues. LDL rather than HDL may be used as the preferential source of cholesterol for steroidogenesis in human adult adrenocortical cells.