Blood Cholesterol and Hydrocortisone Production in Man: Quantitative Aspects of the Utilization of Circulating Cholesterol by the Adrenals at Rest and under Adrenocorticotropin Stimulation*

Borkowski, Abraham; Levin, Sam; Delcroix, Claude; Mahler, A.; Verhas, Vera

doi:10.1172/jci105580

Cited by 83 publications

(37 citation statements)

References 25 publications

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“…The fi rst and rate-limiting step is the formation of pregnenolone from cholesterol. At rest and during stress about 80 % of circulating cortisol is derived from plasma cholesterol: the remaining 20 % is synthesized in situ from acetate and other precursors 91 . Experimental studies suggest that HDL is the preferred cholesterol source of steroidogenic substrate in the adrenal gland 92 .…”

Section: Clinical Consequences Of Hypocholesterolemiamentioning

confidence: 99%

Hypocholesterolemia in Clinically Serious Conditions - Review

Vyroubal¹,

Chiarla²,

Giovannini³

et al. 2008

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background:Cholesterol is an essential component of cell membranes, precursor of steroids, biliary acids and other components of serious importance in live organism. Cholesterol synthesis is a complicated and energy-demanding process. Real daily need of cholesterol and mechanisms of decline cholesterol levels in critical ill are unknown. During stressful situations a signifi cant hypocholesterolaemia may be found. Hypocholesterolemia has been known for a number of years to be a signifi cant prognostic indicator of increased morbidity and mortality connected with a whole spectrum of pathological conditions. The aim of article is the elucidation of the role and importance of hypocholesterolaemia during the intensive care. . Methods and Results:We examined studies that are engaged in problems of hypocholesterolemia in critically ill. Very low levels of total as well as LDL cholesterol are most frequently found in serious polytrauma, after extensive surgery, in serious infections, in protracted hypovolemic shock. It is still not clear whether hypocholesterolemia refl ects only a serious metabolic disorder, which results from a life-threatening condition, or whether it has an active role in evolution and outcome.Conclusions: Hypocholesterolemia is commonly observed in critically ill patients. Nevertheless, it is not known whether it is a secondary manifestation of disease, or whether it actively contributes to deterioration of the disease. Although the contribution of hypocholesterolemia to mortality is modest compared with known risk factors such as increased severity of illness and the development of nosocomial infection, low serum lipid concentrations represent a potential therapeutic target in sepsis.

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Section: Clinical Consequences Of Hypocholesterolemiamentioning

confidence: 99%

Hypocholesterolemia in Clinically Serious Conditions - Review

Vyroubal¹,

Chiarla²,

Giovannini³

et al. 2008

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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“…Adrenal tissue may serve as a useful model for studying these mechanisms because studies in man (1,2) and the rat (3,4) showed that 80% or more of the cholesterol substrate for adrenal steroidogenesis may come from plasma. However, little is known about the process by which extracellular cholesterol enters the adrenal cells.…”

mentioning

confidence: 99%

Adrenal cholesterol uptake from plasma lipoproteins: regulation by corticotropin.

Gwynne¹,

Mahaffee²,

Brewer³

et al. 1976

Proc. Natl. Acad. Sci. U.S.A.

128

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The transfer of lipoprotein-bound cholesterol into adrenal cells was examined. Adrenal glands from unstimulated or corticotropin stimulated hypophysectomized rats were incubated with high density lipoprotein (HDL) or low density lipoprotein LDL containing radiolabeled cholesterol. The rate of transfer of labeled cholesterol from HDL into the glands was two to three times greater than from LDL. Corticotropin stimulation increased the transfer of cholesterol from HDL but not LDL. The effects of corticotropin were not dependent on subsequent cholesterol utilization for steroidogenesis. The process of cholesterol transfer from HDL was linear with time over 2 hr at 370 and greatly reduced at 40. In addition, the transfer process became saturated above an HDL cholesterol concentration of 900 sg/ml. About 25% of the labeled adrenal cholesterol arising from HDL was recovered within the mitochondria. The labeled cholesterol within isolated mitochondria could undergo mitochondrial conversion to pregnenolone. Finally, the delipidated HDL apolipoproteins, apoA-I and apoA-II, when added to incubations containing less than saturating concentrations of HDL, stimulated transfer of labeled cholesterol from HDL to adrenal cells. These studies suggest that rat adrenal tissue possesses an HDL specific hormonally-responsive mechanism for accumulating extracellular cholesterol and that apoA-I and apoA-II have a significant function in the uptake process.The mechanisms responsible for transferring cholesterol from plasma into cells are of particular interest because of their possible role in atherosclerotic disease. Adrenal tissue may serve as a useful model for studying these mechanisms because studies in man (1, 2) and the rat (3, 4) showed that 80% or more of the cholesterol substrate for adrenal steroidogenesis may come from plasma. However, little is known about the process by which extracellular cholesterol enters the adrenal cells. Dexter et al. (4) have observed that the uptake process is stimulated by corticotropin (adrenocorticotrophic hormone, ACTH), and furthermore that the stimulatory effect of ACTH persists even when utilization of accumulating cholesterol is blocked by specific inhibitors.Serum cholesterol is lipoprotein bound, predominantly by the high density lipoprotein (HDL) and low density lipoprotein (LDL) fractions. In the rat (5), 60% of the circulating cholesterol is found in HDL and 30% in LDL, while in man 30% and 60% are found in HDL and LDL, respectively (6). In order to better understand the uptake of cholesterol by adrenal cells as well as ACTH regulation of the uptake process, we have examined the ability of HDL and LDL to serve as substrate for transfer of cholesterol to the adrenal. The observations reported here suggest that HDL is the preferred substrate for adrenal cholesterol uptake, and that uptake from HDL is regulated by ACTH. Furthermore, these studies suggest that the HDL apoproteins, apoA-I and apoA-II, play a role in the cholesterol uptake process. Table legends. Incubations were p...

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“…Moreover in man (Borkowski, Levin, Delcroix, Mahler & Verhas, 1967) and in the guinea-pig (Werbin & Chaikoff, 1961) it was demonstrated that the proportion of cholesterol derived from the plasma at rest, 80% in man and 60% in the guinea-pig, was not altered by administration of ACTH. Oestrogen treatment does decrease plasma cholesterol concentrations (Boyd & McGuire, 1956) and the resulting hypofunction of the adrenal during stress can be instantaneously restored to normal by intravenous infusion of plasma from normal but not from hexoestrol treated rats (Holzbauer & Vogt, 1957a).…”

Section: Discussionmentioning

confidence: 99%

“…Oestrogen treatment does decrease plasma cholesterol concentrations (Boyd & McGuire, 1956) and the resulting hypofunction of the adrenal during stress can be instantaneously restored to normal by intravenous infusion of plasma from normal but not from hexoestrol treated rats (Holzbauer & Vogt, 1957a). To the author's knowledge there are no reports on the effect of ACTH on plasma cholesterol levels, but since ACTH has been shown to accelerate the metabolism of plasma and adrenal cholesterol into hydrocortisone (Borkowski et al, 1967) and not to stimulate cholesterol synthesis, a decrease in plasma cholesterol might be expected.…”

Section: Discussionmentioning

confidence: 99%

The actions of ethinyloestradiol on the pituitary‐adrenal system of the rat

1970

British J Pharmacology

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Summary1. Single doses of ethinyloestradiol stimulate the pituitary adrenal axis of the female rat during quiescent conditions. 2. After a stimulus which releases endogenous ACTH, there is an inhibition of the release of corticosterone from the adrenal gland, but an increase in the corticosterone stored in the gland.3. Ethinyloestradiol (1V0 mg/kg) injected acutely or daily for 7 days does not affect the corticosterone bindinlg capacity of plasma in female rats, or the clearance rate of an injection of corticosterone. 4. Prolonged treatment with ethinyloestradiol and ACTH inhibits the pituitary-adrenal response to a stress and to an ACTH injection, indicating a block at the adrenal and pituitary level. 5. The adrenal gland recovers more rapidly than the pituitary after cessation of the oestrogen treatment. 6. The inhibition of the pituitary-adrenal response to stress after oestrogen is probably caused by inhibition of cholesterol synthesis as suggested by others. Oestrogens can increase corticoid secretion during non-stress conditions, however, so precursor lack through exhaustion cannot be excluded. 7. It is suggested that the inhibition of the stress response after prolonged ACTH treatment is due to a decrease in sensitivity of the adrenal cortex after frequent ACTH stimulation, but the possibility that it is due to a reduction in circulating cholesterol cannot be ruled out.

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Blood Cholesterol and Hydrocortisone Production in Man: Quantitative Aspects of the Utilization of Circulating Cholesterol by the Adrenals at Rest and under Adrenocorticotropin Stimulation*

Cited by 83 publications

References 25 publications

Hypocholesterolemia in Clinically Serious Conditions - Review

Hypocholesterolemia in Clinically Serious Conditions - Review

Adrenal cholesterol uptake from plasma lipoproteins: regulation by corticotropin.

The actions of ethinyloestradiol on the pituitary‐adrenal system of the rat

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