Separate mechanisms for the uptake of high and low density lipoproteins by mouse adrenal gland in vivo

The adrenal gland of the mouse exhibits uptake mechanisms for plasma high density lipoprotein (HDL) and low density lipoprotein (LDL). To study this uptake, we lowered the endogenous plasma lipoprotein level in mice by administering 4-aminopyrazolopyrimidine and then injected the animals with tracer amounts of human ¹²⁵I-HDL or ¹²⁵I-LDL intravenously. Uptake of ¹²⁵I-HDL and ¹²⁵I-LDL in the adrenal gland was demonstrable within 2 min after injection, and the content of radioactivity reached a steady state within 30 min. The adrenal gland accumulated 20-fold more ¹²⁵I radioactivity/mg of tissue than lung or kidney. Moreover, the adrenal took up 50- to 200-fold more ¹²⁵I-HDL or ¹²⁵I-LDL than ¹²⁵I-albumin. Adrenal uptake of both lipoproteins was reduced when adrenocorticotrophic hormone secretion was suppressed by dexamethasone. Uptake of either LDL or HDL raised the level of cholesteryl esters in the adrenal gland and suppressed the activity of microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase. The uptake mechanisms were saturable in that unlabeled lipoproteins competed with the ¹²⁵I-lipoproteins for uptake. In cross-competition experiments, unlabeled LDL competed more effectively than unlabeled HDL for ¹²⁵I-LDL uptake; conversely, unlabeled HDL competed more effectively than unlabeled LDL for ¹²⁵I-HDL uptake. These data suggest that two different lipoprotein uptake systems supply cholesterol to the adrenal gland of the mouse, one using LDL and another using HDL.