Disruption of steroidogenesis: Cell models for mechanistic investigations and as screening tools

Abstract

In the modern world, humans are exposed during their whole life to a large number of synthetic chemicals. Some of these chemicals have the potential to disrupt endocrine functions and contribute to the development and/or progression of major diseases. Every year approximately 1000 novel chemicals, used in industrial production, agriculture, consumer products or as pharmaceuticals, are reaching the market, often with limited safety assessment regarding potential endocrine activities. Steroids are essential endocrine hormones, and the importance of the steroidogenesis pathway as a target for endocrine disrupting chemicals (EDCs) has been recognized by leading scientists and authorities. Cell lines have a prominent role in the initial stages of toxicity assessment, i.e. for mechanistic investigations and for the medium to high throughput analysis of chemicals for potential steroidogenesis disrupting activities. Nevertheless, the users have to be aware of the limitations of the existing cell models in order to apply them properly, and there is a great demand for improved cell-based testing systems and protocols. This review intends to provide an overview of the available cell lines for studying effects of chemicals on gonadal and adrenal steroidogenesis, their use and limitations, as well as the need for future improvements of cell-based testing systems and protocols.

Keywords: Adrenal; Endocrine disrupting chemical; Granulosa; In vitro; Leydig; Ovary; Testis.