Exposure to 4-tert-octylphenol accelerates sexual differentiation and disrupts expression of steroidogenic factor 1 in developing bullfrogs.

ABSTRACT

Sex-specific gonadal steroidogenesis during development is critical to differentiation of the sexually dimorphic phenotype and reproductive function of adult organisms. Environmental contaminants may affect the process of sexual differentiation through disruption of steroid production and/or action. Control of the steroidogenic metabolic pathway is regulated partly by P450 cytochrome hydroxylases, and the expression of many of these enzymes is controlled by the orphan nuclear receptor, steroidogenic factor-1 (SF-1). In mammals, SF-1 expression is critical for development of the reproductive axis and adult reproductive function. In the bullfrog Rana catesbeiana, during sequential stages of development encompassing sexual differentiation, SF-1 protein expression becomes elevated in ovaries of sexually differentiating females, whereas expression in testes decreases. We exposed tadpoles to the industrial pollutant octylphenol (OP) for 24 hr before and during the critical stages of sexual differentiation to determine whether this known endocrine disruptor affects sex differentiation and SF-1 expression. We found that both females and males treated with an environmentally relevant low dose (10(-9)M) of OP underwent early gonadal differentiation. Furthermore, OP exposure disrupted the sexually dimorphic expression of SF-1 that occurs during sexual differentiation. Our results suggest that OP exposure may affect developmental processes that could ultimately influence adult reproductive function and that these disruptive effects may be mediated in partly through disturbances in gene regulation by SF-1.