The Roles of Calcium-dependent Signal Transduction and Environmental Xenobiotic Chemicals in Modulating Ovarian Steroidogenesis in SciaenidsEPA Grant Number: U915731
Title: The Roles of Calcium-dependent Signal Transduction and Environmental Xenobiotic Chemicals in Modulating Ovarian Steroidogenesis in Sciaenids
Investigators: Benninghoff, Abby Diane
Institution: The University of Texas at Austin
EPA Project Officer: Klieforth, Barbara I
Project Period: August 1, 2000 through August 1, 2003
Project Amount: $83,931
RFA: STAR Graduate Fellowships (2000) RFA Text | Recipients Lists
Research Category: Fellowship - Environmental Toxicology , Academic Fellowships , Health Effects
The goal of this research project is to investigate xenobiotic chemical disruption of calcium-dependent signaling as a potential novel mechanism of endocrine disruption in the Atlantic croaker (Micropogonias undulatus) and spotted seatrout (Cynoscion nebulosus), two sciaenid species inhabiting coastal areas in the Gulf of Mexico. The importance of calcium signaling in hormonal control of ovarian steroid production has been demonstrated in numerous vertebrate species. Therefore, the specific objectives for this research project are to: (1) characterize the calcium-dependent signaling pathways regulating ovarian steroid production, and (2) investigate xenobiotic chemical alteration of these calcium signaling pathways.
The first phase of research involves the characterization of calcium-dependent signal transduction in ovarian steroidogenic cells. Specific pharmacological drugs, such as calcium channel blockers, calcium ionophores and calmodulin inhibitors, will be used in in vitro static incubation of ovarian tissue to elucidate the role of specific components in calcium signaling pathways regulating ovarian steroid production. A primary cell culture system will be developed for Atlantic croaker ovarian steroidogenic cells to directly measure changes in intracellular calcium concentrations in response to hormone treatments. The second phase of research will investigate xenobiotic disruption of calcium-dependent signal transduction and subsequent alteration of ovarian steroidogenesis. Preliminary experiments will study effects of xenobiotic chemicals on normal endocrine function by screening a variety of compounds including heavy metals, pesticides, and polychlorinated biphenyls (PCBs). Compounds causing significant alteration in steroid production in the preliminary assays will be selected for continued experiments to elucidate whether the chemical is altering endocrine function by modifying calcium-dependent signal transduction. In vitro ovarian tissue incubations will be used to assess effects of contaminants on ovarian steroidogenesis, and ovarian steroidogenic cells in primary culture will be used to determine direct effects of xenobiotics on calcium homeostasis.
Alternative mechanisms of endocrine disruption will be identified and bioassays will be developed to identify the chemicals acting by these parthways.