A secretory protease inhibitor requires androgens for its expression in male sex accessory tissues but is expressed constitutively in pancreas.
A full length cDNA clone encoding a mouse prostatic secretory glycoprotein (p12) whose synthesis is dependent upon testicular androgens has been cloned and characterized. The predicted amino acid sequence of p12 shares extensive homology with several members of the Kazal family of secretory protease inhibitors, in particular the pancreatic secretory trypsin inhibitors. In agreement with sequence data, prostatic secretory p12, purified from mouse ventral prostate secretion, exhibits anti-trypsin activity. Steady-state levels of protease inhibitor mRNA in ventral prostate are reduced from approximately 0.06% in normal mice to undetectable after androgen withdrawal but are inducible within 4 h by re-administration of testosterone. Androgen-dependent expression of the secretory protease inhibitor mRNA was also observed in coagulating gland and seminal vesicle. In seminal vesicle, a tissue of different embryonic origin to the prostate, the kinetics of secretory protease inhibitor mRNA loss after castration are not as rapid as in the ventral prostate and coagulating gland. Low-level androgen independent expression was also observed in the pancreas. There appears to be a single gene for this secretory protease inhibitor and yet expression is markedly stimulated by testosterone in the sex accessory tissues and unaffected by this hormone in the pancreas.
Molecular Endocrinology Laboratory, Imperial Cancer Research Fund, London, UK.
J S
JS
Mills
M
M
Needham
M G
MG
Parker
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D005796:Genes / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009919:Orchiectomy; D010179:Pancreas / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism*; D029584:Prostatic Secretory Proteins; D011480:Protease Inhibitors / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D013739:Testosterone / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D002352:Carrier Proteins; D029584:Prostatic Secretory Proteins; D011480:Protease Inhibitors; C028321:estramustine-binding protein; D013739:Testosterone