Neural and Interrenal Steroidogenesis as Cellular and Molecular Targets for Emerging Fluorinated organochemicals and Pharmaceutical EDCs.

Endocrine disruptor testing strategies have omitted examination of the neural and adrenal glands and do not adequately cover the process of steroidogenesis. Steroidogenesis is critical for adrenocortical, testicular and ovarian functions, and represents m ultiple molecular targets for toxicity, ranging from general effects on all steroidogenic tissues (e.g. via StAR protein, cholesterol side-chain cleavage, P450scc or CYP17) through to specific targets affecting only adrenocortical function (e.g. CYP11b/18 and glucocorticoid synthesis) or gonadal functions (17b-hydroxysteroid dehydrogenase/aromatase and androgen/estrogen synthesis). For adequate and comprehensive assessment of a compound for endocrine disruption, it is necessary to examine the entire endoc rine system. These will include all the glands, hormonal target tissues, receptors, synthesis enzymes, hormones and carrier proteins, etc. that comprise the system as a whole. Therefore, the main objectives of the present project proposal is to quantitati vely and mechanistically evaluate the effects of a pharmaceutical (ethnylestradiol) and perfluorinated organochemical (PFOS) on gene expression patterns of all key neural and interrenal steroidogenic proteins and enzymes using modern molecular techniques in Atlantic salmon. Special emphasis will be given to the rate-limiting steps involving steroidogenic acute regulatory (StAR) protein and the cytochrome P450 mediated cholesterol side-chain cleavage enzyme (P450scc; Figure 1). Despite having a toxicologic al and endocrine starting point, data from this study will play significant roles in the understanding of salmon endocrinology with practical aquaculture implication for this species and can be adapted for other freshwater and marine species.