Screening and Testing Methods and Endpoints for Evaluating Endocrine Disruptors 3-1 3. Gonadotropin Releasing Hormone:Gonadotropin:Sex Steroid Signaling Pathway

1. In vertebrates, reproduction is primarily controlled by the HPG axis and, the structure of this endocrine pathway is highly conserved in jawed vertebrates (gnathostoma). The hypothalamic neuroendocrine system regulates synthesis and release of the gonadotropins, follicle-stimulating-hormone (FSH) and LH, from the pituitary, which in turn stimulate gonadal development, in particular via the induction of sex steroid synthesis. Sex steroids feedback to the hypothalamus and the pituitary, thereby regulating gonadotropin synthesis and release (Kanda et al., 2011; Thackray et al., 2010). In addition, non-steroidal feedback regulation of gonadotropins by FSH-stimulated gonadal inhibins contributes to the synchronization of the HPG axis at all stages of the life cycle (de Kretser et al., 2002; Thackray et al., 2010). In lower vertebrates such as fish, the activin/inhibin system plays a role in paracrine regulation of gonadal function, and also an autocrine/paracrine activin system in the fish pituitary has been demonstrated. Furthermore, endocrine feedback of gonad-derived activin/inhibin on gonadotropins has been suggested. However, the involvement of inhibins in the regulation of pituitary gonadotropins as true endocrine hormones of gonadal origin, which circulate in the blood stream, has yet to be demonstrated in fish.