Metabolism of adrenal cholesterol in man

Borkowski, Abraham; Delcroix, Claude; Levin, Sam

doi:10.1172/jci106969

Cited by 24 publications

(2 citation statements)

References 25 publications

(18 reference statements)

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“…(J Clin Endocrinol Metab 58: 206, 1984) T HE BIOSYNTHESIS of adrenal corticosteroids is dependent upon a continuous supply of cholesterol, which can be derived from two potential sources: synthesis with the gland and uptake of plasma lipoproteins (1)(2)(3)(4)(5)(6). Receptor-mediated uptake of low density lipoproteins (LDL) provides an important source of cholesterol for corticosteroid synthesis by human adrenocortical cells grown in tissue culture.…”

mentioning

confidence: 99%

Adrenocortical Response to Adrenocorticotropin in Heterozygous Familial Hypercholesterolemia*

Illingworth

Alam

Lindsey

1984

The Journal of Clinical Endocrinology & Metabolism

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Receptor-mediated uptake of low density lipoproteins (LDL) provides an important source of cholesterol for corticosteroid synthesis by human adrenocortical cells grown in tissue culture. Recent studies have indicated an impaired adrenocortical response to prolonged ACTH stimulation in patients with abetalipoproteinemia (who lack plasma LDL) and in patients with homozygous familial hypercholesterolemia (FH), who have a virtual absence of high affinity LDL receptors. In the present study we examined parameters of adrenocortical function in four women with well characterized heterozygous FH to assess whether a 50% reduction in the number of LDL receptors measured in vitro influenced the response of the adrenal cortex to prolonged stimulation with ACTH. Biochemical studies of the binding, internalization, and degradation of [125I]LDL were undertaken in cultured skin fibroblasts from each patient, and all patients had reduced LDL receptor activity. The adrenocortical response to a 36-h iv infusion of alpha ACTH-(1-24) (Cortrosyn) was evaluated in the four patients with heterozygous FH and in five normal women. Stimulation with iv ACTH resulted in rapid increases in the serum concentrations of cortisol in both groups and plateau concentrations of 55-60 micrograms/dl. The rates of increase and the plateau concentrations were similar in the control and FH patients. Similarly, rates of excretion of 17-hydroxycorticosteroids and cortisol were similar in the normal subjects and FH patients. These results indicate that a 50% reduction in the number of high affinity LDL receptors due to the presence of one abnormal gene at the LDL receptor locus does not result in any impairment in the delivery of cholesterol to the adrenal cortex during conditions of maximal corticosteroid production.

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confidence: 99%

Adrenocortical Response to Adrenocorticotropin in Heterozygous Familial Hypercholesterolemia*

Illingworth

Alam

Lindsey

1984

The Journal of Clinical Endocrinology & Metabolism

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“…I N ALL animal species so far studied, the bulk of the cholesterol used for the synthesis of steroid hormones in the adrenal cortex originates from plasma (1)(2)(3)(4)(5)(6). Recently, the mechanism by which the adrenal gland takes up plasma cholesterol has begun to be explored.…”

mentioning

confidence: 99%

Low Density Lipoprotein Receptors in Bovine Adrenal Cortex. I. Receptor-Mediated Uptake of Low Density Lipoprotein and Utilization of Its Cholesterol for Steroid Synthesis in Cultured Adrenocortical Cells*

et al. 1979

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Functioning bovine adrenocortical cells in monolayer culture were shown to obtain cholesterol for steroid synthesis from plasma low density lipoprotein (LDL). When grown in medium devoid of lipoproteins, the cells developed a minimal enhancement in steroid secretion in response to ACTH or cholera toxin. However, when LDL was available, steroid secretion was stimulated 4- to 9-fold. To determine the mechanism for this effect, we used LDL in which the protein component was labeled with 125I and the cholesteryl ester component was labeled with [3H]cholesteryl linoleate. These studies demonstrated that the cells derived cholesterol from LDL by binding the lipoprotein at a high affinity receptor site, internalizing it, and hydrolyzing its cholesteryl esters within lysosomes. The resultant free cholesterol was used for steroid synthesis and also acted to suppress the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol synthesis within the cell. LDL receptor activity was enhanced several-fold by treatment of the cells with ACTH or cholera toxin. High density lipoprotein, which did not bind to the LDL receptor, was not degraded with high affinity by the cells and did not support steroid synthesis. The current data suggest that the bovine adrenal cortex can obtain cholesterol for steroid hormone secretion from circulating LDL by means of a high affinity LDL receptor pathway. In a subsequent paper in this series, a similar high affinity LDL-binding site is demonstrated in membranes prepared from fresh bovine adrenocortical tissue.

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Cholesterol Metabolism in Man

Sodhi¹

1975

Hypolipidemic Agents

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Metabolism of adrenal cholesterol in man

Cited by 24 publications

References 25 publications

Adrenocortical Response to Adrenocorticotropin in Heterozygous Familial Hypercholesterolemia*

Adrenocortical Response to Adrenocorticotropin in Heterozygous Familial Hypercholesterolemia*

Low Density Lipoprotein Receptors in Bovine Adrenal Cortex. I. Receptor-Mediated Uptake of Low Density Lipoprotein and Utilization of Its Cholesterol for Steroid Synthesis in Cultured Adrenocortical Cells*

Cholesterol Metabolism in Man

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