Interactions of xenobiotics with the steroid hormone biosynthesis pathway

Abstract

Environmental contaminants can potentially disrupt endocrine processes by interfering with the function of enzymes involved in steroid synthesis and metabolism. Such interferences may result in reproductive problems, cancers, and toxicities related to (sexual) differentiation, growth, and development. Various known or suspected endocrine disrupters interfere with steroidogenic enzymes. Particular attention has been given to aromatase, the enzyme responsible for the conversion of androgens to estrogens. Studies of the potential for xenobiotics to interfere with steroidogenic enzymes have often involved microsomal fractions of steroidogenic tissues from animals exposed in vivo, or in vitro exposures of steroidogenic cells in primary culture. Increasingly, immortalized cell lines, such as the H295R human adrenocortical carcinoma cell line are used in the screening of effects of chemicals on steroid synthesis and metabolism. Such bioassay systems are expected to play an increasingly important role in the screening of complex environmental mixtures and individual contaminants for potential interference with steroidogenic enzymes. However, given the complexities in the steroid synthesis pathways and the biological activities of the hormones, together with the unknown biokinetic properties of these complex mixtures, extrapolation of in vitro effects to in vivo toxicities will not be straightforward and will require further, often in vivo, investigations.