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Acute Statin Administration Reduces Levels of Steroid Hormone Precursors.
London, Edra; Tatsi, Christina; Soldin, Steven J; Wassif, Christopher A; Backlund, Peter; Ng, David; Biesecker, Leslie G; Stratakis, Constantine A.
Afiliação
  • London E; Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland, USA.
  • Tatsi C; Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland, USA.
  • Soldin SJ; Department of Laboratory Medicine, NIH, Bethesda, Maryland, USA.
  • Wassif CA; Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland, USA.
  • Backlund P; Biomedical Mass Spectrometry Core, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland, USA.
  • Ng D; Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
  • Biesecker LG; Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
  • Stratakis CA; Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland, USA.
Horm Metab Res ; 52(10): 742-746, 2020 Oct.
Article em En | MEDLINE | ID: mdl-32040961
ABSTRACT
Cholesterol-lowering statin drugs are used by approximately 25% of US adults 45 years of age and older and frequency of use is even higher among the elderly. Cholesterol provides the substrate for steroid hormone synthesis and its intracellular concentrations are tightly regulated. Our aim was to evaluate whether statin use acutely changes the circulating levels of cortisol, other glucocorticoid precursor molecules and their metabolites. Fourteen subjects not taking statins were administered a single oral dose (2 mg) of pitavastatin. Blood samples collected at baseline and 24 h post-treatment were analyzed for plasma cholesterol and steroid hormone profile. A parallel study in mice entailed the administration of atorvastatin (10 mg/kg) via orogastric delivery for three consecutive days. Cholesterol and corticosterone levels were quantified at baseline and at 1-day and 1-week post-treatment. Several precursor molecules in the steroidogenic pathway (corticosterone, cortisone, and 11-deoxycortisol) were significantly decreased 24 h after administration of a single dose of pitavastatin in human study subjects. Their circulating cholesterol concentrations were unchanged. In mice, there were no significant differences in serum cholesterol or corticosterone at 1-day or 1-week post-treatment compared to both pre-treatment baseline levels and control group levels. We conclude that acute dysregulation of the production of certain glucocorticoid precursor molecules was observed after a single treatment with a lipophilic statin drug. This may be of clinical relevance for individuals with underlying or subclinical adrenal insufficiency.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Hormônios Esteroides Gonadais / Colesterol / Inibidores de Hidroximetilglutaril-CoA Redutases / Glucocorticoides Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Hormônios Esteroides Gonadais / Colesterol / Inibidores de Hidroximetilglutaril-CoA Redutases / Glucocorticoides Idioma: En Ano de publicação: 2020 Tipo de documento: Article