The hypothalamic-pituitary-gonadal axis is target of cadmium toxicity. An update of recent studies and potential therapeutic approaches.

This review presents an overview of neuroendocrine disruption induced by cadmium on the hypothalamic-pituitary-gonadal (HHG) axis. This review focuses on a number of hypotheses: (1) the HHG axis is a physiological target on cadmium toxicity; (2) cadmium could induce chronotoxicity on this neuroendocrine axis by disrupting the daily pattern of the HHG axis activity; (3) cadmium exposure throughout life could contribute to the oxidative stress and the circadian rhythms disruption induced by aging on the HHG; and (4) cadmium induces oxidative stress in the HHG axis so antioxidants could prevent or reduce cadmium toxicity in this system. Cadmium disrupts the regulatory mechanisms of this physiological axis, by altering neurotransmitters involved in this regulation at the hypothalamic level, altering gonadotropin hormone secretion, and by affecting testicular or ovarian structure and activity. These effects are age-dependent and they could be related to the circadian rhythms of this physiological axis. Several antioxidant agents could have a protective action against the neuroendocrine toxicity of cadmium on the reproductive system. A comprehensive view of the physiological axis may provide a better understanding about the neuroendocrine toxicity of cadmium on the reproductive system, so this perspective is recommended for undertaking further studies.