Regulation of steroid synthesis

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.

Steroid isolation , depending on context, is the isolation of chemical matter required for chemical structure elucidation, derivitzation or degradation chemistry, biological testing, and other research needs (generally milligrams to grams, but often more [37] or the isolation of "analytical quantities" of the substance of interest (where the focus is on identifying and quantifying the substance (for example, in biological tissue or fluid). The amount isolated depends on the analytical method, but is generally less than one microgram. [38] [ page needed ] The methods of isolation to achieve the two scales of product are distinct, but include extraction , precipitation, adsorption , chromatography , and crystallization . In both cases, the isolated substance is purified to chemical homogeneity; combined separation and analytical methods, such as LC-MS , are chosen to be "orthogonal"—achieving their separations based on distinct modes of interaction between substance and isolating matrix—to detect a single species in the pure sample. Structure determination refers to the methods to determine the chemical structure of an isolated pure steroid, using an evolving array of chemical and physical methods which have included NMR and small-molecule crystallography . [2] :10–19 Methods of analysis overlap both of the above areas, emphasizing analytical methods to determining if a steroid is present in a mixture and determining its quantity. [38]

Regulation of steroid synthesis

regulation of steroid synthesis


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