Journal of Clinical Endocrinology & Metabolism, Vol 64, 531-535, Copyright © 1987 by Endocrine Society

ARTICLES

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

L Laue, JM Hoeg, K Barnes, DL Loriaux and GP Chrousos

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 coenzyme 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.

This article has been cited by other articles:

				B. P. Schimmer, M. Cordova, H. Cheng, A. Tsao, A. B. Goryachev, A. D. Schimmer, and Q. Morris Global Profiles of Gene Expression Induced by Adrenocorticotropin in Y1 Mouse Adrenal Cells Endocrinology, May 1, 2006; 147(5): 2357 - 2367. [Abstract] [Full Text] [PDF]

				W. A Prescott Jr, D.-a. D Streetman, and D. S Streetman The Potential Role of HMG-CoA Reductase Inhibitors in Pediatric Nephrotic Syndrome Ann. Pharmacother., December 1, 2004; 38(12): 2105 - 2114. [Abstract] [Full Text] [PDF]

				A. Rigotti, H. E. Miettinen, and M. Krieger The Role of the High-Density Lipoprotein Receptor SR-BI in the Lipid Metabolism of Endocrine and Other Tissues Endocr. Rev., June 1, 2003; 24(3): 357 - 387. [Abstract] [Full Text] [PDF]

				T. Ishii, T. Hasegawa, C.-I Pai, N. Yvgi-Ohana, R. Timberg, L. Zhao, G. Majdic, B.-c. Chung, J. Orly, and K. L. Parker The Roles of Circulating High-Density Lipoproteins and Trophic Hormones in the Phenotype of Knockout Mice Lacking the Steroidogenic Acute Regulatory Protein Mol. Endocrinol., October 1, 2002; 16(10): 2297 - 2309. [Abstract] [Full Text] [PDF]

				J. Liu, R. Voutilainen, P. Heikkila, and A. I. Kahri Ribonucleic Acid Expression of the CLA-1 Gene, a Human Homolog to Mouse High Density Lipoprotein Receptor SR-BI, in Human Adrenal Tumors and Cultured Adrenal Cells J. Clin. Endocrinol. Metab., August 1, 1997; 82(8): 2522 - 2527. [Abstract] [Full Text] [PDF]

				A. Rigotti, E. R. Edelman, P. Seifert, S. N. Iqbal, R. B. DeMattos, R. E. Temel, M. Krieger, and D. L. Williams Regulation by Adrenocorticotropic Hormone of the in Vivo Expression of Scavenger Receptor Class B Type I (SR-BI), a High Density Lipoprotein Receptor, in Steroidogenic Cells of the Murine Adrenal Gland J. Biol. Chem., December 27, 1996; 271(52): 33545 - 33549. [Abstract] [Full Text] [PDF]

				B. Staels, G. Martin, M. Martinez, C. Albert, J. Peinado-Onsurbe, R. Saladin, D. W. Hum, M. Reina, S. Vilaro, and J. Auwerx Expression and Regulation of the Lipoprotein Lipase Gene in Human Adrenal Cortex J. Biol. Chem., July 19, 1996; 271(29): 17425 - 17432. [Abstract] [Full Text] [PDF]

				F. J. Dowell, C. A. Hamilton, G. B. M. Lindop, and J. L. Reid Development and Progression of Atherosclerosis in Aorta From Heterozygous and Homozygous WHHL Rabbits : Effects of Simvastatin Treatment Arterioscler. Thromb. Vasc. Biol., August 1, 1995; 15(8): 1152 - 1160. [Abstract] [Full Text]