Androgen regulation of an elastase-like protease activity in the seminal vesicle.
The processing of secretory proteins in the guinea pig (GP) seminal vesicle epithelium (SVE) is altered by castration and restored by treatment of animals with androgens. To test the hypothesis that the changes in protein processing are due to changes in the activity of specific proteases, we examined the GPSVE for protease activities capable of cleaving a synthetic elastase substrate, succinyl-alanyl-alanyl-alanyl-p-nitroanilide (Suc(Ala)3pNA). We found that the GPSVE does contain a Suc(Ala)3pNA-cleaving activity that is sensitive to the serine protease inhibitor diisopropylfluorophosphate (DFP) and to the elastase inhibitor elastatinal. Furthermore, the amount of protease activity per milligram of SVE protein is reduced to about 50% of control levels by castration. The activity is completely restored within four days by treatment of castrated animals with androgens, but is not restored by treatment with estradiol, progesterone, or dexamethasone. Although the SVE enzyme did not yield a pattern of specific cleavage products when incubated with a secretory protein substrate in vitro, this enzyme activity was competitively inhibited by a peptide whose primary sequence included the cleavage site used by the processing machinery in vivo.
Harvey
S
S
Department of Biochemistry and Molecular Biology, Mayo Foundation, Rochester, Minnesota 55905, USA.
Vrabel
A
A
Smith
S
S
Wieben
E
E
D000595:Amino Acid Sequence; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D002863:Chromogenic Compounds / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology; D006168:Guinea Pigs; D007531:Isoflurophate / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D009919:Orchiectomy; D010196:Pancreatic Elastase / Q000378:metabolism*; D012669:Seminal Vesicles / Q000187:drug effects / Q000201:enzymology*; D013739:Testosterone / Q000494:pharmacology
D000728:Androgens; D002863:Chromogenic Compounds; D009842:Oligopeptides; D007531:Isoflurophate; D013739:Testosterone; C015516:succinyl-trialanine-4-nitroanilide; D010196:Pancreatic Elastase