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.
Actemra/RoActemra is the only approved anti-IL-6 receptor biologic, available in both intravenous (IV) and subcutaneous formulations, for the treatment of adult patients with moderate to severe active rheumatoid arthritis (RA). Actemra/RoActemra can be used alone or with methotrexate (MTX) in adults who are intolerant to, or have failed to respond to, other anti-rheumatic medications. In the most recent update to the European League Against Rheumatism (EULAR) RA management guidelines, Actemra/RoActemra is highlighted as the only biologic that has been repeatedly demonstrated to be superior as a monotherapy over MTX or other conventional disease-modifying antirheumatic drugs (DMARDs). Actemra/RoActemra IV formulation is approved in most major countries for polyarticular juvenile idiopathic arthritis (pJIA) and systemic juvenile idiopathic arthritis (sJIA) in children two years of age and older. In Europe, Actemra/RoActemra is also approved for use in patients with severe, active and progressive RA who previously have not been treated with MTX. Actemra/RoActemra is part of a co-development agreement with Chugai Pharmaceutical Co., Ltd and has been approved in Japan since April 2005. Actemra/RoActemra is approved in more than 100 countries worldwide.