ABSTRACT
Hormones of a particular endocrine axis have been used experimentally and clinically to modulate toxic insult against a component gland within the same endocrine axis. For example, hormones from the hypothalamo-pituitary-gonadal axis have been used to ameliorate testicular toxicity. Glode et al. (1981) reported that a GnRH analogue (D-Leu6 GnRH) could protect against cyclophosphamide-induced testicular damage in mice. There have been similar reports in rat and dog and this has led to the suggestion that the use of GnRH analogues may be useful in a clinical setting for the protection of the testes in cancer chemotherapy (reviewed in Garside & Harvey 1992). Sex steroids are also known to protect the testes from toxic insult: in the mouse, both progesterone (Wolkowski-Tyl & Preston 1979) and oestrogen (Gunn et al. 1965) are protective against the necrotizing effects of cadmium to the testes. Other structurally-related steroids, such as the natural and synthetic glucocorticoids corticosterone and dexamethasone, are without such effect, and the necrotizing potential of cadmium to the testes and other organs and tissues is not modulated by these compounds, at least in the mouse (Wolkowski-Tyl & Preston 1979). In the rat, however, progesterone does not protect the testes from cadmium, indeed the reverse is true since progesterone has been reported to significantly exacerbate and enhance cadmium toxicity, especially to the liver (Shiraishi et al. 1993). Thus, different steroids with structural similarity but differing pharmacological activity can modulate toxicity in different ways and this is species-dependent.
