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LACK OF EXPRESSION OF EGF AND TGF-ALPHA IN THE FETAL MOUSE ALTERS FORMATION OF PROSTATIC EPITHELIAL BUDS AND INFLUENCES THE RESPONSE TO TCDD
Citation:
Abbott, B D., T. M. Lin, N. T. Rasmussen, R. W. Moore, R. M. Albrecht, J E. Schmid, AND R. E. Peterson. LACK OF EXPRESSION OF EGF AND TGF-ALPHA IN THE FETAL MOUSE ALTERS FORMATION OF PROSTATIC EPITHELIAL BUDS AND INFLUENCES THE RESPONSE TO TCDD. TOXICOLOGICAL SCIENCES 76(2):427-436, (2003).
Description:
Lack of Expression of EGF and TGF in the Fetal Mouse Alters Formation of Prostatic Epithelial Buds and Responsiveness to TCDD-Induced Impairment of Prostatic Bud Formation.
Barbara D. Abbott, Tien-Min Lin, Nathan T. Rasmussen, Robert W. Moore,
Ralph M. Albrecht, Judith E. Schmid, and Richard E. Peterson
ABSTRACT
In utero 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure causes abnormal ventral, dorsolateral and anterior prostate development in C57BL/6 mice. Androgens, mesenchymal-epithelial interactions and growth factor expression all have roles in initiating and regulating development and growth of the prostate. Epidermal growth factor (EGF) and transforming growth factor alpha (TGF ), both of which bind the EGF receptor (EGFR), are expressed in human and rodent developing prostate. This study examines the influence of null expression of EGF and/or TGF on prostatic bud development and on the ability of TCDD to inhibit prostatic budding. Growth factor knockout (-/-) and wild type (WT) mice were exposed either to vehicle or to TCDD (0, 0.2, 1, 5, 10, 50, 100 or 150 g/kg) on GD12. The number anterior, dorsal, and lateral prostatic buds (ADLB) and ventral buds (VB) were counted on GD17.5. In control TGF (-/-) fetuses, the number of ADLBs were stimulated relative to the WT. Control EGF+TGF (-/-) had poor bud outgrowth, especially in the ADL region. TCDD induced a dose-related decrease in bud formation in all strains, however the severity of the response was affected by growth factor expression, with the most severe effects in the EGF+TGF (-/-) fetuses. TGF (-/-) and C57BL/6J fetuses responded to TCDD similarly. In conclusion, EGF and TGF expression are important for the formation of ADLBs and VBs and expression of EGF and TGF affects the ability of TCDD to inhibit prostatic bud formation in a region-specific manner.