Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Addition of rat or human high density lipoproteins (HDL) or human low density lipoproteins (LDL) to rat adrenocortical cells in vitro was found to enhance steroid production and increase cell cholesterol content. These effects of HDL were not observed in cultured mouse Y-1 adrenal cells, suggesting that rat adrenal cells possess a specific mechanism for uptake of HDL cholesterol not found in Y-1 cells. The effects of HDL were most marked on cells previously stimulated with adrenocorticotropin (ACTH) and depleted of their endogenous cholesterol stores. Such cells were prepared either by treatment in vivo with 4-aminopyrazolopyrimidine or in vitro with ACTH (10(-7) M) in lipoprotein-poor media. Steroid production by treated cells exhibited a saturable dependence on media HDL concentration. In addition to enhancing ACTH stimulated steroid production, addition of HDL also resulted in a saturable concentration-dependent increase in cell cholesterol content. Both aminoglutethimide and cycloheximide were found to inhibit HDL-enhanced steroid production. Finally, addition of HDL to short term incubations (5 1/2 h) of ACTH-treated cells caused no change in the rate of incorporation of 14C-acetate into cholesterol or corticosterone. These results indicate that rat adrenocortical cells possess a specific, saturable, ACTH-dependent mechanism for uptake of HDL cholesterol. Moreover, cellular uptake of HDL cholesterol exceeded by at least 4-fold the amount of cholesterol associated with HDL apoprotein degraded by the cells, suggesting that utilization of HDL cholesterol does not require endocytosis and lysosomal degradation of the entire HDL particle.
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PMID:The role of high density lipoproteins in rat adrenal cholesterol metabolism and steroidogenesis. 625 90

Changes in the morphology of rat adrenal cortex with age include increased accumulations of lipid droplets and lipofuscin granules. Because glandular concentrations of cholesteryl esters (CE) and apolipoprotein (apo) E are also increased in parallel, the utilization or metabolism of lipid-droplet stored CE for steroidogenesis might be altered in aging cells. To explore this possibility, adrenocortical cholesterol storage and utilization were studied in 3-6 months-old (mo) (Y) rats and 20-23 mo (O) Fischer 344 male rats. Both groups received either adrenocorticotropin (ACTH1-39, Acthar gel) or gelatin alone daily for seven consecutive days. We found that: (a) the CE concentration in O rats, but not Y animals, was diminished by ACTH. The depleted CE in stimulated-O rats was replenished within five days post stimulation. Failure to deplete CE in stimulated-Y rats was not associated with an insufficient dose of the hormone, since stimulation of Y animals with higher doses of ACTH actually increased the CE concentration. In contrast, adrenocortical free cholesterol concentration remained constant during stimulation regardless of age. (b) The depleted CE in stimulated-O rats was principally comprised of cholesteryl adrenate, cholesteryl arachidonate and cholesteryl cervonate. The accumulated CE in stimulated-Y animals was primarily comprised of cholesteryl adrenate, cholesteryl arachidonate and cholesteryl oleate. (c) Whereas in stimulated-Y rats adrenal apoE concentration declined, the concentration in stimulated O animals was well maintained. (d) In vitro, adrenal homogenate or cytosolic fraction from stimulated-O rats displayed a higher capacity to hydrolyze exogenous CE than its Y counterpart. However, cholesterol esterification with external fatty acid substrates in adrenal homogenate or microsomal fraction was comparable in the two age-groups. Our findings revealed altered adrenocortical cholesterol reserve in O rats to cope with prolonged ACTH-stimulation. Changes in apoE levels and CE hydrolysis activity may be factors associated with this alteration. Depletion and accumulation of adrenocortical CE are reflected in parallel changes in cholesteryl adrenate and cholesteryl arachidonate, suggesting physiologic importance of these polyunsaturated fatty acids during sustained steroidogenesis.
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PMID:Effects of prolonged ACTH-stimulation on adrenocortical cholesterol reserve and apolipoprotein E concentration in young and aged Fischer 344 male rats. 974 39

Administration of adrenocorticotropic hormone (ACTH) has been shown to decrease plasma concentrations of apolipoprotein B (apoB) containing lipoproteins, including lipoprotein(a), in man. However, the mechanism behind this hypolipidemic effect is unknown. This study aimed at distinguishing between the main possibilities (increased elimination or decreased production of lipoproteins) using HepG2 cell cultures. Addition of ACTH to the cell culture medium selectively down-regulated apoB mRNA expression and apoB secretion in a dose-dependent manner. At 100 pmol/liter ACTH, the apoB mRNA level was about 40% lower than in the untreated cells, and the secretion of apoB into the medium was decreased to a similar extent. The expression and secretion of other apolipoproteins (apoA-I, apoE, and apoM), however, were not affected by ACTH. Under normal culture conditions the level of secretion of apoB from HepG2 cells is quite low. In the presence of 0.4 mmol/liter oleic acid secretion of apoB increased 3-fold, but this phenomenon was not seen in ACTH-treated cells. Binding and internalization of radiolabeled low density lipoprotein (LDL) by HepG2 cell, as well as LDL-receptor mRNA and scavenger receptor B-I mRNA levels, were not influenced by ACTH. In conclusion, ACTH directly and selectively down-regulated the production and secretion of apoB in HepG2 cell cultures, suggesting that a principal mechanism behind the cholesterol-lowering effect of ACTH in vivo may be a decreased production rate of apoB-containing lipoproteins from the liver.
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PMID:ACTH decreases the expression and secretion of apolipoprotein B in HepG2 cell cultures. 1151 56

Previous studies suggest the hypothesis that apoE produced by adrenocortical cells modulates cellular cholesterol metabolism to enhance the storage of esterified cholesterol (EC) at the expense of cholesterol delivery to the steroidogenic pathway. In the present study, parameters of adrenal cholesterol metabolism and corticosteroid production were examined in wild type and apoE-deficient (apoe(-/-)) mice. Adrenal gland EC content and the EC/free cholesterol (FC) ratio in mice stressed by adrenocorticotropin (ACTH) treatment or saline injection were reduced in apoe(-/-) compared to apoe(+/+) mice. Relative to apoe(+/+) mice, apoE deficiency also resulted in increased levels of plasma corticosterone in the basal state, in response to acute or long-term ACTH treatment, and after a swim-induced neuroendocrine-directed stress test. Measurements of adrenal gland scavenger receptor class B, type I (SR-BI), LDL receptor, and LDL receptor related protein (LRP) levels and the activities of ACAT or HMG-CoA reductase showed no difference between genotypes. Apoe(-/-) and apoe(+/+) mice showed similar quantitative increases in LDL receptors, SR-BI, adrenal weight gain, and ACAT activities in response to ACTH, and both genotypes had similar basal plasma ACTH concentrations. These results suggest that the effects of apoE deficiency reflect events at the level of the adrenal gland and are specific to changes in cholesterol accumulation and corticosterone production. Further, these findings support the hypothesis that apoE acts to enhance adrenocortical EC accumulation and diminish corticosterone production.
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PMID:Altered adrenal gland cholesterol metabolism in the apoE-deficient mouse. 1240 91