TY - JOUR
T1 - Impaired adrenal reserve in the Watanabe heritable hyperlipidemic rabbit
T2 - Implications for LDL-receptor function in steroidogenesis
AU - Hoeg, Jeffrey M.
AU - Loriaux, Lynn
AU - Gregg, Richard E.
AU - Green, William R.
AU - Brewer, H. Bryan
N1 - Funding Information:
From the Molecular Disease Branch. the National Heart, Lung, and Blood Institute, the Developmental Endocrinology Branch, Child Health and Human Development, and the Laboratory of Pathology, National Cancer Institute, National Institutes of Health. Bethesda, h4d. Address reprint requests to Jeflrey M. Hoeg. MD. Bldg 10, Room 7NI I7, National Institutes of Health, Bethesda, MD 20205. Q 1985 by Grune & Stratton, Inc. 0026-0495/85/3302~15$03.00/0
PY - 1985/2
Y1 - 1985/2
N2 - The cholesterol required for steroidogenesis may be provided by de novo biosynthesis or through the delivery of cholesterol by the circulating lipoproteins. By studying adrenocortical function, structure and biosynthetic capacity in an animal model devoid of the classical, high-affinity low-density lipoprotein (LDL) receptor pathway, the respective roles of de novo cholesterolgenesis and lipoprotein cholesterol delivery were investigated. The Watanabe Heritable Hyperlipemic (WHHL) rabbit lacks the LDL-receptor pathway. The activity of the rate-limiting enzyme in cholesterolgenesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was 4- to 15-fold greater than normal in the WHHL adrenal gland. The basal corticosterone concentrations were normal in the WHHL rabbit; however, the corticosterone concentration increased by less than 50% of normal after an intravenous ACTH injection. Electron-microscopic evaluation of adrenocortical cells from the WHHL rabbits disclosed significantly increased mitochondrial surface area and diminished amounts of cytosolic lipid and lysosomal area. These data indicate that the mammalian adrenal gland utilizes endogenously synthesized cholesterol as well as cholesterol delivered through the LDL-receptor pathway. Moreover, in the absence of the LDL-receptor pathway, endogenously produced cholesterol is sufficient for normal basal glucocorticoid function.
AB - The cholesterol required for steroidogenesis may be provided by de novo biosynthesis or through the delivery of cholesterol by the circulating lipoproteins. By studying adrenocortical function, structure and biosynthetic capacity in an animal model devoid of the classical, high-affinity low-density lipoprotein (LDL) receptor pathway, the respective roles of de novo cholesterolgenesis and lipoprotein cholesterol delivery were investigated. The Watanabe Heritable Hyperlipemic (WHHL) rabbit lacks the LDL-receptor pathway. The activity of the rate-limiting enzyme in cholesterolgenesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was 4- to 15-fold greater than normal in the WHHL adrenal gland. The basal corticosterone concentrations were normal in the WHHL rabbit; however, the corticosterone concentration increased by less than 50% of normal after an intravenous ACTH injection. Electron-microscopic evaluation of adrenocortical cells from the WHHL rabbits disclosed significantly increased mitochondrial surface area and diminished amounts of cytosolic lipid and lysosomal area. These data indicate that the mammalian adrenal gland utilizes endogenously synthesized cholesterol as well as cholesterol delivered through the LDL-receptor pathway. Moreover, in the absence of the LDL-receptor pathway, endogenously produced cholesterol is sufficient for normal basal glucocorticoid function.
UR - http://www.scopus.com/inward/record.url?scp=0022002672&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0022002672&partnerID=8YFLogxK
U2 - 10.1016/0026-0495(85)90132-5
DO - 10.1016/0026-0495(85)90132-5
M3 - Article
C2 - 3969018
AN - SCOPUS:0022002672
VL - 34
SP - 194
EP - 197
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
SN - 0026-0495
IS - 2
ER -