Gregg D, Goedken E, Gaikin M, Wendell D, Gorski J
Department of Biochemistry and Animal Science, University of Wisconsin, Madison 53706, USA.
Mol Cell Endocrinol. 1996 Mar 25;117(2):219-25. doi: 10.1016/0303-7207(95)03750-0.
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.
在前体蛋白转化酶PC2和PC3等内肽酶切割肽前体之后，羧肽酶E（CPE）发挥作用，从各种垂体激素的C末端去除碱性氨基酸。我们研究了CPE在大鼠品系对雌激素诱导的垂体肿瘤的不同敏感性中的作用。在抗肿瘤的斯普拉格-道利（SD）大鼠中，己烯雌酚（DES）对垂体CPE蛋白水平没有影响。然而，在易患肿瘤的费希尔344（F344）大鼠中，DES降低了CPE蛋白水平，以至于在治疗7周和8周时，几乎检测不到CPE。停用DES一周后，8周时CPE蛋白水平增加。DES治疗2周和4周后，F344大鼠的CPE蛋白水平分别降至对照值的18%和2.3%，但在前体蛋白转化酶2（PC2）或PC3的蛋白水平上未观察到品系差异。此外，用DES对棕色挪威（BN）大鼠、F344大鼠和F1杂种（BN×F344）大鼠进行10周治疗。DES对BN大鼠的垂体CPE蛋白水平没有影响，而F344大鼠的垂体CPE蛋白水平仅为BN大鼠的8%。对DES有中等体重反应的F1大鼠的垂体，其CPE蛋白水平处于中等水平（为BN大鼠的31%）。在SD大鼠中，DES对CPE mRNA水平没有影响，而在F344大鼠中，DES在治疗2周和4周后均倾向于降低CPE mRNA水平，尽管反应存在差异。因此，似乎在抗肿瘤大鼠和F344大鼠之间，垂体CPE蛋白主要在转录后水平受到DES的不同调节。此外，在F344大鼠中CPE蛋白水平与DES治疗引起的垂体重量增加呈负相关。
