Using mirex, an organochlorine compound, it is possible to initiate an adaptive liver growth response which is either hyperplastic or hypertrophic. That is, hyperplastic liver growth is induced in mirex-dosed adrenalectomized rats and hypertrophic liver growth is induced in mirex-dosed thyroidectomized rats. Previous studies have shown that the mirex-induced hypertrophic growth response is corticosterone dependent and the mirex-induced hyperplastic growth response is corticosterone independent. The objective of the proposed research is to investigate the role of corticosterone in mediating mirex-induced adaptive liver growth. To accomplish this, studies are proposed to investigate: transport/delivery of corticosterone to the liver by analyses of free and bound plasma corticosterone and corticosteroid-binding globulin; the unidirectional influx of corticosterone into the liver; hepatic cytosolic glucocorticoid receptor binding and characterization of hepatic binding proteins as the initial step in corticosterone's control of liver growth; and, hepatic tyrosine aminotransferase induction as a measure of the liver's responsiveness to corticosterone during mirex-induced liver growth. Mirex-induced adaptive liver growth provides an in vivo model to: establish the basic sequence of events involved in initiation of cellular hypertrophy, and/or hyperplasia; provide an understanding of the mechanism of induction of these two basic cellular responses; and, give insight into the mechanism of chemically- induced tumor growth. The proposed studies will also provide a means to characterize the role of the endocrine system in controlling chemically-induced stress responses at the cellular level.
| Yarbrough, J D; Grimley, J M; Thottassery, J V (1992) Mirex-induced adaptive liver growth in rats subjected to thyroidectomy. Hepatology 15:923-7 |
| Thottassery, J V; Yarbrough, J D (1991) Regulation of glucocorticoid receptors during adaptive liver growth. Am J Physiol 260:G603-9 |
| Yarbrough, J; Cunningham, M; Yamanaka, H et al. (1991) Carbohydrate and oxygen metabolism during hepatocellular proliferation: a study in perfused livers from mirex-treated rats. Hepatology 13:1229-34 |
