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(818) NEONATAL DIETHYLSTILBESTROL-INDUCED DISRUPTION OF SPECIFIC PROTEIN EXPRESSION IN THE HAMSTER UTERUS: CONTINUED SCREENING FOR EARLY vs. LATE EFFECTS. Hendry, William1, Alwis, Imala1, 1 Department of Biological Sciences, Wichita, KS ABSTRACT- The synthetic estrogen, diethylstilbestrol (DES), is an established endocrine disruptor. In the hamster, neonatal DES administration rapidly and permanently disrupts the developing uterus (early, initiation stage) such that the adult uterus responds abnormally to natural ovarian estrogens (late, promotion stage). As part of a campaign to define the mechanisms of both the initiation and promotion phases of the disruption phenomenon, we use immunoblotting to: 1) screen newly acquired antibodies from various sources for immunoreactivity in the hamster uterine system, and 2) determine if levels of cognate antigens are altered at the whole-organ level in DES-exposed uteri. Undergraduate students, supported by a NIH-funded scholarship program, have performed the bulk of such analyses. Of the antibodies evaluated by a recent student, the most noteworthy findings about reactive antigens were as follows: 1) Transcriptional Intermediary Factor 1 beta (TIF1b) is a transcriptional co-repressor known to play essential roles in chromatin remodeling and early embryonic development. The 110-kDa antigen was highly expressed only in the initiation-stage uteri but the level of expression was not affected by neonatal DES exposure. 2) p63 protein is a homolog of the tumor suppressor p53 gene product and is reported to coordinate anogenital modeling and epithelial cell differentiation in the developing female urogenital tract. In initiation-stage uteri, the 64-kDa antigen was upregulated by neonatal DES exposure. In contrast, the antigen in promotion-stage uteri was downregulated by neonatal DES exposure. 3) p21-Activated Kinase-1 (Pak1) is one of three isoforms of serine/threonine kinases and is reported to phosphorylate/transactivate estrogen receptor alpha and promote hyperplasia in mammary epithelium. Neonatal DES exposure resulted in expression of the 40-kDa antigen being upregulated in initiation-stage uteri but downregulated in promotion-stage uteri. These results provide further insight into the extent to which neonatal DES exposure affects proteomics in the hamster uterus. They also provide guidance for the choice of immunoreagents that could be used to study/screen the cell and tissue-specific consequences of perinatal exposure to DES and other putative endocrine disruptor agents. KEY WORDS: uterus, proteomics, endocrine disruption, diethylstilbestrol |
