Xénohormones : mode d'action et effets suspectés.

Abstract

Les effets des agents polluants de l' environnement, comme les pesticides et les herbicides, sur la sante humaine et animale ont fait l' objet de nombreux travaux ces dernieres annees, et ont suscite des craintes qui ont ete evoquees meme dans la presse a grand public. Le mode d' action le plus souvent propose de ces xenobiotiques est leur capacite d' interagir avec les recepteurs des hormones steroides, notamment ceux des oestrogenes, et a declencher ainsi une reponse inappropriee dans le temps et dans l' espace. Cette inquietude a ete renforcee par l' exemple " historique " d' un medicament, le diethylstilbestrol, un mimetique de l' oestradiol, qui provoque l' apparition de cancers genitaux chez les filles exposees in utero. Cependant, la nocivite reelle de ces xenobiotiques de l' environnement est toujours un sujet de controverse, certains auteurs estimant qu' ils n' atteignent pas dans l' organisme des concentrations necessaires a la manifestation de leurs effets xenohormonaux. Neanmoins, les tres nombreux travaux experimentaux sur le sujet ont ouvert un nouveau champ d' investigation sur le mode d' action des xenobiotiques qui devrait etre confronte aux donnees cliniques et epidemiologiques.

During the last few years, several chemical compounds that are environmental pollutants have been shown to display xenohormonal activity, and have been called endocrine disrupters. In particular, several pesticides and herbicides bind the estrogen receptor and activate oestradiol-dependent gene promoters. It has been suggested that these compounds could account for the increase in both the male reproductive disorders as well as the incidence of testicular cancer. This hypothesis which remains controversial, is strenghthened by the well known toxic effects in human and in animals of the drug diethyl stilbestrol, an estrogen mimetic. Xeno-estrogens could act during fetal life by altering the organogenesis of the reproductive system or by disrupting the gonadotropin-steroid hormones feedback loop. Other xenobiotics could act through their anti-androgenic activity or by modifying the metabolism or the half-life of the steroid hormones. Since endocrine disrupters could prove to be harmful to man and animals, several in vivo or in vitro tests have been developped to assay for their functional activity. [References: 46]