The influence of adrenocorticotropin on transport of a cholesteryl linoleate-low density lipoprotein complex into adrenal tumor cells

The action of adrenocorticotropin (ACTH) on the specific (receptor-mediated) uptake of cholesteryl linoleate·low density lipoprotein complexes was examined in Y-1 mouse adrenal tumor cells. High affinity binding (KA 4.1 x 10⁸ M) was observed with ACTH; lower affinity was seen in the absence of ACTH. The effect of ACTH was observed within 10 min at physiological concentrations of low density lipoprotein (100 μg/ml). Binding was followed by uptake (internalization) of the ester·lipoprotein complex which was transported to lysosomes. The site of action of ACTH was localized to the uptake process (internalization) since no effect of ACTH was observed on binding to the cell membrane nor on movement of internalized complex to lysosomes. ACTH increases the transport of cholesterol derived from cholesterol ester to the mitochondria. This cholesterol is converted to 20α-hydroxypregn-4-en-3-one and this conversion is accelerated by ACTH. Dibutyryl cyclic AMP (but not butyrate) also stimulates uptake of cholesteryl linoleate·low density lipoprotein. The process stimulated by ACTH and dibutyryl cyclic AMP is specific for low density (as opposed to high density) lipoprotein and for ACTH as distinct from other peptide hormones. The possible physiological importance of this response is considered.