Various environmental-and industrial chemicals can perturb male reproductive function. The objectives of these studies are to define subcellular target sites in testicular somatic cells in primary culture. For FY88, efforts have focused on effects of mono-2-ethylhexyl-phthalate, delta 9 tetrahydrocannabinol, and the active metabolite of tri-o-cresyl phosphate (TOCP), saligenin cyclic o-tolyl phosphate, on Sertoli cells in primary culture. Since TOCP needs to be metabolized to an active intermediate in vivo, and because the testis has more of this active metabolite than most other tissues in the body, studies have been initiated to evaluate the capability of Leydig cells to activate TOCP in vitro, and to investigate the relationship of this activation to the Sertoli cell response to the saligenin in vitro. Endpoints for these studies have included overall energy balance, intermediary metabolism control, and """"""""throughput,"""""""" enzyme activity, cytoskeletal distribution by immunostaining. The emphasis continues to be on the dose- and time-relationships between these endpoints. Second messengers (cyclic AMP, calcium, and inositol trisphosphate) are important regulators of cellular function. We have recently initiated a series of studies to determine whether testicular toxicants exert some of their effects by altering these second messenger systems. Compounds for these studies are the same as above: MEHP and delta 9 tetrahydrocannabinol. The significance of these studies is that they have identified structures and processes within these somatic testicular cells which are vulnerable to toxicants. A greater knowledge of where and how compounds work will further our understanding of how the cells work, and could help avoid toxicity for novel compounds in the future.
