Steroid regulation of drug-metabolizing cytochromes P450

K. Monostory, Zdenek Dvorak

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Cytochrome P450 (P450) monooxygenases are capable of catalyzing metabolism of various endogenous and exogenous compounds, such as bile acids, fatty acids, retinoids, steroids, drugs and other xenobiotics. The enzymes, belonging to CYP1, CYP2 and CYP3 families are primarily involved in the metabolism of drugs and xenobiotics. P450-mediated defense mechanism protects organisms from the potentially toxic effects of xenobiotics to which they are exposed. The adaptive transcriptional induction of P450s by xenobiotics is mediated by aromatic hydrocarbon receptor of Per-ARNT-Sim family, and nuclear hormone receptors, including pregnane X receptor, constitutive androstane receptor and glucocorticoid receptor. In addition to the receptor-mediated induction, endogenous factors (developmental, sex or hormonal factors) can also modulate P450 expression. Steroid hormones are biologically active compounds, controlling many physiological processes via endocrine signaling pathways and contributing to the transcriptional regulation of drugmetabolizing P450s. Any change in P450 activities influences the rate of activation or inactivation of drugs. Exposure to xenobiotics (drugs, environmental pollutants) can exert changes in endocrine function both directly as hormone agonists/antagonists or indirectly altering the rates of hormone metabolism and consequently the circulating levels of hormones. Modulation of P450 expression by xenobiotics can affect the subsequent metabolism of not only foreign chemicals, but also steroid hormones. Perturbation in hormone metabolism leads to the imbalance in sexual and reproductive development, and in glucose, lipid and salt/water homeostasis. The purpose of this review is to highlight the interplay between drug-metabolizing P450s and steroid hormones as well as the interactions of xenosensor with steroid signaling pathways.

Original languageEnglish
Pages (from-to)154-172
Number of pages19
JournalCurrent Drug Metabolism
Volume12
Issue number2
DOIs
Publication statusPublished - Feb 2011

Fingerprint

Drug and Narcotic Control
Xenobiotics
Cytochrome P-450 Enzyme System
Metabolism
Steroid hormones
Steroids
Hormones
Pharmaceutical Preparations
Physiological Phenomena
Hormone Antagonists
Sex Factors
Aromatic Hydrocarbons
Environmental Pollutants
Sexual Development
Saline water
Poisons
Glucocorticoid Receptors
Retinoids
Defense Mechanisms
Cytoplasmic and Nuclear Receptors

Keywords

  • Androgens
  • Cytochrome P450
  • Estrogens
  • Glucocorticoids
  • Hormonal regulation
  • Nuclear receptors
  • Steroid hormones
  • Steroid receptors

ASJC Scopus subject areas

  • Pharmacology
  • Clinical Biochemistry

Cite this

Steroid regulation of drug-metabolizing cytochromes P450. / Monostory, K.; Dvorak, Zdenek.

In: Current Drug Metabolism, Vol. 12, No. 2, 02.2011, p. 154-172.

Research output: Contribution to journalArticle

Monostory, K. ; Dvorak, Zdenek. / Steroid regulation of drug-metabolizing cytochromes P450. In: Current Drug Metabolism. 2011 ; Vol. 12, No. 2. pp. 154-172.
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