Effect of age on cholesterol uptake and utilization by rat adrenals: I. Internalization of lipoprotein-derived cholesteryl esters.
Previous studies from this laboratory have documented a progressive age-related decline in trophic hormone (or second messenger cAMP) stimulated corticosterone production in isolated adrenocortical cells. In the current study, we examined the possibility that the aging process exerts this effect by interfering with an early step in the delivery of lipoprotein-derived cholesteryl esters to the cell. As such, we monitored the ability of two different rat adrenocortical cell model systems (intact perfused adrenal glands and primary cultures of adrenocortical cells from 5- and 18- to 20-month-old rats) to internalize lipoprotein cholesteryl esters, and to convert the newly internalized cholesteryl esters to corticosterone production. The results indicate that lipoprotein (hHDL3 and rHDL) cholesteryl ester internalization (by both the endocytic and 'selective' pathways) is comparable in adrenocortical cells of the young and old rats. However, despite this, both the mass of corticosterone produced and the ratio of newly internalized (radiolabeled) cholesteryl ester incorporated into corticosterone is dramatically reduced in cells of the older animals. Thus, the lipoprotein uptake pathway appears to be intact in adrenals of older rats, but the intracellular processing of internalized cholesteryl ester is defective.
Azhar
S
S
Geriatrics Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Palo Alto, CA 94304, USA.
Reaven
E
E
D000225:Adenine / Q000031:analogs & derivatives; D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000924:Anticholesteremic Agents; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism*; D003345:Corticosterone / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000924:Anticholesteremic Agents; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; C004420:4-aminopyrazolo(3,4-d)pyrimidine; C014409:cholesteryl oleate; D002784:Cholesterol; D000225:Adenine; D003345:Corticosterone