The effect of mevinolin on steroidogenesis in patients with defects in the low density lipoprotein receptor pathway

L. Laue, J. M. Hoeg, K. Barnes, Donald (Lynn) Loriaux, G. P. Chrousos

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Abstract

Adrenal steroidogenesis is dependent upon cholesterol derived from both de novo biosynthesis and uptake of plasma lipoproteins through the low density lipoprotein (LDL) receptor pathway. Recent studies have demonstrated that patients homozygous for familial hypercholesterolemia have a mild impairment in cortisol secretion during maximal ACTH stimulation. Mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzye A reductase, has been used clinically to inhibit de novo cholesterol synthesis in patients with familial hypercholesterolemia. In this study we examined hypothalamic-pituitary-adrenal function in seven patients with defects in the LDL receptor pathway, both before and during treatment with oral mevinolin (20 mg, twice a day), to assess whether inhibition of cholesterol synthesis influences steroidogenesis under basal conditions and in response to ovine CRH and exogenous ACTH. Two months after initiation of therapy, high density lipoprotein cholesterol levels were significantly elevated, and LDL cholesterol levels were reduced, although not normalized. Basal and ovine CRH-stimulated adrenocortical function were normal in all patients both before and during therapy. Plateau plasma cortisol concentrations achieved during maximal ACTH stimulation were lower than those in control subjects in all patients both before and during therapy. All patients, however, had an approximately 3-fold increase over basal values. These results suggest that treatment of patients with defects in the LDL receptor pathway with mevinolin improves the plasma lipid profile and does not result in adrenal dysfunction or further exacerbation of the mild impairment of adrenal function during maximal ACTH stimulation.

Original languageEnglish (US)
Pages (from-to)531-535
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume64
Issue number3
StatePublished - 1987
Externally publishedYes

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Lovastatin
LDL Receptors
Adrenocorticotropic Hormone
Defects
Cholesterol
Plasmas
Hydrocortisone
Hyperlipoproteinemia Type II
Biosynthesis
Sheep
LDL Cholesterol
HDL Cholesterol
Lipoproteins
Oxidoreductases
Therapeutics
Lipids

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

The effect of mevinolin on steroidogenesis in patients with defects in the low density lipoprotein receptor pathway. / Laue, L.; Hoeg, J. M.; Barnes, K.; Loriaux, Donald (Lynn); Chrousos, G. P.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 64, No. 3, 1987, p. 531-535.

Research output: Contribution to journalArticle

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