Ribonucleic Acid Expression of the CLA-1 Gene, a Human Homolog to Mouse High Density Lipoprotein Receptor SR-BI, in Human Adrenal Tumors and Cultured Adrenal Cells¹

Abstract

Human CLA-1 is homologous to the mouse SR-BI gene, which was recently identified as a high density lipoprotein receptor involved in selective cholesterol uptake in rodent adrenal cells. We screened 42 normal and pathological adrenal samples by Northern blotting and found abundant expression of CLA-1 messenger ribonucleic acid (mRNA) in normal adult and fetal adrenals, adrenocortical adenomas, and hyperplasias. Adrenocortical carcinomas and the adrenals adjacent to Cushing's adenomas contained less CLA-1 mRNA than normal adrenals. CLA-1 mRNA was also highly expressed in a Leydig cell tumor, but much less in liver, kidney, and pheochromocytomas. The accumulation of CLA-1 mRNA in primary cultures of normal adrenocortical cells was up-regulated by ACTH in a dose- and time-dependent manner. Both dibutyryl cAMP and staurosporine increased the basal expression of CLA-1 mRNA. Although there was no additive effect of ACTH and dibutyryl cAMP, staurosporine slightly enhanced the stimulatory effect of ACTH on the expression of CLA-1 mRNA. The abundant expression of CLA-1 mRNA and its regulation by the physiological hormone ACTH in human adrenal cells suggest that CLA-1 has a role in adrenal steroidogenesis, probably as a lipoprotein receptor mediating the selective cholesterol uptake in these cells.

Adrenocortical LDL receptor function negatively influences glucocorticoid output

“…Adrenals express high levels of scavenger receptor BI (SR-BI; Acton et al 1996, Liu et al 1997, the sole mediator of the selective cholesteryl ester uptake from HDLs (Out et al 2004). In addition, expression of the LDL receptor (LDLR) has also been detected on glucocorticoid-producing cells of the adrenal zona fasciculata (Fong et al 1989).…”