Environmental endocrine disrupters and disorders of sexual differentiation.

Endocrine disrupters are exogenous substances that cause adverse effects in the endocrine system. Sexual differentiation is regulated by reproductive hormones. Male differentiation is critically dependent on normal androgen action, which in turn depends on normal production of luteinizing hormone. Other essential hormones include follicle-stimulating hormone, anti-Müllerian hormone, and insulin-like hormone 3 (insl-3). Estrogens influence transcription of insl-3 and affect sexual differentiation both directly and indirectly. Diethylstilbestrol is the best known endocrine disrupter and has caused abnormalities of sexual differentiation in both exposed male and female human fetuses. There is a growing group of chemicals that have weak estrogenic properties, but, in addition, there are several antiandrogenic compounds that have been shown to disturb sexual differentiation in experimental animals. It is a challenge for endocrinologists to find out whether or not these chemicals or mixtures of them are involved in any of the abnormalities of human sexual differentiation.