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.
Gregg
D
D
Department of Biochemistry and Animal Science, University of Wisconsin, Madison 53706, USA.
Goedken
E
E
Gaikin
M
M
Wendell
D
D
Gorski
J
J
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D043423:Carboxypeptidase H; D002268:Carboxypeptidases / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000139:chemically induced / Q000378:metabolism; D045706:Proprotein Convertase 2; D043484:Proprotein Convertases; D012333:RNA, Messenger; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013381:Subtilisins / Q000378:metabolism; D013997:Time Factors
D004968:Estrogens, Non-Steroidal; D012333:RNA, Messenger; D004054:Diethylstilbestrol; D002268:Carboxypeptidases; D043423:Carboxypeptidase H; D043484:Proprotein Convertases; D013381:Subtilisins; D045706:Proprotein Convertase 2; D016282:Aspartic Acid Endopeptidases