Yeast pheromone signaling pathway as a bioassay to assess the effect of chemicals on mammalian peptide hormones

Abstract

The intercellular pheromone signal transduction pathways involved in sexual reproduction in the yeast Saccharomyces cerevisiae constitute an extracellular network system involving cell surface receptors. The system is analogous to the signaling pathway of mammalian peptide hormones. The yeast mating pheromone α factor is homologous to mammalian gonadoliberins such as luteinizing hormone-releasing hormone (LHRH). In this study, we used the yeast pheromone signaling pathway as a model system to evaluate the effect of industrial chemicals on mammalian peptide hormones. Haploid a- and α-cell types conjugate, using mating pheromones, to form diploid cells. However, in a cells treated with certain chemicals used in pesticides, fungicides, and industrial products (i.e., TPN (CAS No. 1897-45-6), thiuram (CAS No. 137-26-8), captan (CAS No. 133-06-2), oxine–copper (CAS No. 10380-28-6), zineb (CAS No. 12122-67-7), and ziram (CAS No. 137-30-4)) the induction of shmoo formation was suppressed even when commercial α-factor was added. The FUS1–lacZ gene, which is transcriptionally regulated by a pheromone, was transferred into yeast and the effects of TPN, captan, zineb, and ziram, under sublethal conditions, were investigated: β-Galactosidase levels declined to levels similar to that of untreated control cells when in the absence of the α-factor. Furthermore, these chemicals influenced conjugation to α-cells, and mating efficiency declined as chemical concentration increased. Analysis of the yeast pheromone signaling pathway helps to establish chemical toxicity assay models for mammalian peptide signal transduction pathways.