Interactions of xenobiotics with the steroid hormone biosynthesis
pathway
T. Sanderson and M. van den Berg
Institute for Risk Assessment Science, Utrecht University,P.O.Box
8017, 3508 TD Utrecht, The Netherlands
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.
*Report from a SCOPE/IUPAC project: Implication of
Endocrine Active Substances for Human and Wildlife (J. Miyamoto and
J.Burger, editors). Other reports are published in this issue,
pp. 1617-2615.
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