Decreased expression of carboxypeptidase E protein is correlated to estrogen-induction of rat pituitary tumors.
Following the cleavage of peptide precursors by endopeptidases such as the proprotein convertases PC2 and PC3, carboxypeptidase E ( CPE) functions to remove basic amino adds from the C-terminus of various pituitary hormones. We investigated the role of CPE in the differential sensitivity between rat strains to estrogen-induced pituitary tumors. Pituitary CPE protein levels were unchanged by diethylstilbestrol (DES) in tumor-resistant Sprague-Dawley (SD) rats. However, in tumor-susceptible Fischer 344 (F344) rats, DES decreased CPE protein levels such that by 7 and 8 weeks of treatment, CPE was barely detectable. One week withdrawal of DES caused an increase in CPE protein levels at 8 weeks. After 2 and 4 weeks of DES treatment, CPE protein levels in F344 rats decreased to 18 and 2.3% of control values, respectively, but no strain difference was observed in the protein levels of proprotein convertase 2 (PC2) or PC3. Additionally, Brown Norway (BN), F344, and F1 hybrid (BN x F344) rats were treated with DES for 10 weeks. The level of pituitary CPE protein was not affected by DES in BN rats whereas F344 rats had only 8% of the level of CPE pituitary protein of BN rats. The pituitaries of F1 rats, which had an intermediate weight response to DES, had an intermediate level of CPE protein (31% that of BN rats). Levels of CPE mRNA were not affected by DES in SD rats while in F344 rats DES tended to decrease levels of CPE mRNA after both 2 and 4 weeks of treatment, although the response was variable. It thus appears that pituitary CPE protein is differentially regulated by DES between tumor-resistant rats and F344 rats primarily at the post-transcriptional level. Furthermore, in F344 rats, levels of CPE protein are inversely correlated to increases in pituitary weight caused by DES treatment.[1]References
- Decreased expression of carboxypeptidase E protein is correlated to estrogen-induction of rat pituitary tumors. Gregg, D., Goedken, E., Gaikin, M., Wendell, D., Gorski, J. Mol. Cell. Endocrinol. (1996) [Pubmed]
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