Eppin: a molecular strategy for male contraception.
New male contraceptives, both hormonal and non-hormonal, have many obstacles to overcome before they reach the market as a product. For hormonal contraceptives the long-term efficacy of oligospermia in a large population of unselected men remains to be determined. For nonhormonal contraception target selection remains a primary goal. Immunocontraception, which showed great promise for many years, has recently lost its appeal. Nevertheless, immunocontraception can be utilised as a strategy, particularly in primates, to discern the function of target molecules in the male. As an example, we discuss Eppin, an epididymal protease inhibitor that coats the surface of human spermatozoa. Because Eppin is predicted to be a serine protease inhibitor with chymotrypsin-like specificity and binds semenogelin, the natural substrate of PSA (prostate specific antigen, a serine protease), we investigated whether Eppin would modulate PSA activity and the hydrolysis of semenogelin. Additionally, because antibodies to Eppin provide contraception in male monkeys, we investigated whether antibodies to Eppin would inhibit the PSA hydrolysis of semenogelin. Eppin is a specific inhibitor of PSA activity that requires leucine 87, Eppin's P1 reactive site. Although Eppin modulates the hydrolysis of semenogelin by PSA, antibodies to Eppin do not inhibit PSA activity.
Wang
Zengjun
Z
Department of Cell & Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Widgren
E E
EE
Richardson
R T
RT
Orand
M G
MG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D003269:Contraception, Immunologic / Q000379:methods*; D003272:Contraceptive Agents, Male / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D008297:Male; D011323:Primates; D017430:Prostate-Specific Antigen / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding; D053491:Proteinase Inhibitory Proteins, Secretory / Q000276:immunology*; D012107:Research Design; D012661:Semen / Q000378:metabolism; D029607:Seminal Vesicle Secretory Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D003272:Contraceptive Agents, Male; C431553:Eppin protein, human; D053491:Proteinase Inhibitory Proteins, Secretory; D029607:Seminal Vesicle Secretory Proteins; C424482:seminal vesicle-specific antigen; D017430:Prostate-Specific Antigen