Functional studies of eppin.
Biochem Soc Trans
; 39(5): 1447-9, 2011 Oct.
Article
em En
| MEDLINE
| ID: mdl-21936831
ABSTRACT
Our laboratory has characterized EPPIN [epididymal protease inhibitor; SPINLW1] as a novel gene on human chromosome 20q12-13.2, which encodes a cysteine-rich protein of 133 amino acids with a calculated molecular mass of 15.283 kDa, containing both Kunitz-type and WAP (whey acidic protein)-type four-disulfide core consensus sequences. Eppin is secreted by Sertoli cells in the testis and epididymal epithelial cells; it is predominantly a dimer, although multimers often exist, and in its native form eppin is found on the human sperm surface complexed with LTF (lactotransferrin) and clusterin. During ejaculation SEMG (semenogelin) from the seminal vesicles binds to the eppin protein complex, initiating a series of events that define eppin's function. Eppin's functions include (i) modulating PSA (prostate-specific antigen) enzyme activity, (ii) providing antimicrobial protection and (iii) binding SEMG thereby inhibiting sperm motility. As PSA hydrolyses SEMG in the ejaculate coagulum, spermatozoa gain progressive motility. We have demonstrated that eppin is essential for fertility because immunization of male monkeys with recombinant eppin results in complete, but reversible, contraception. To exploit our understanding of eppin's function, we are developing compounds that inhibit eppin-SEMG interaction and mimic anti-eppin, inhibiting sperm motility. These compounds should have potential as a male contraceptive.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Secretadas Inibidoras de Proteinases
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Biochem Soc Trans
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos