The long term objectives of the proposed studies is to determine the regulation of UDP-glucoronosyl transferase (UDP-GT) inducer-mediated changes in thyroid follicular cell proliferation and apoptosis. This proposal describes a series of experiments that address how these chemicals alter rodent thyroid physiology, both in vivo and in vitro. Preliminary studies with other goitrogens suggest that UDP-GT inducers will effect thyroid follicular cell proliferation and apoptosis. Previous studies have emphasized feedback production of thyroid stimulating hormone (TSH) as the sole contributor to thyroid follicular cell proliferation, and ultimately, thyroid neoplasia. Recent findings such as, 1) while TSH inhibits apoptosis, propylthiouracil (PTU) treatment leads to an induction of apoptosis, and 2) insulin-like growth factor-1 (IGF-1) potently enhances TSH-mediated proliferation, strongly suggest that in addition to TSH that bother"""""""" factors are also important in regulating thyroid follicular cell proliferation and death. The findings from these studies are of importance to human health because there are several therapeutic and environmental agents that induce UDP- GT activity, decrease serum thyroid hormone, and potentially increase serum TSH concentrations. Yet, the relative importance of other factors is unknown. The studies outlined in this proposal will increase the knowledge base in the regulation of thyroid-follicular-cell proliferation and apoptosis, thus, enabling future studies with UDP-GT inducers to accurately assess which changes in thyroid physiology are impor nt.
