The modulation of sperm function by fertilization promoting peptide.
Fertilization promoting peptide (FPP; pGlu-Glu-ProNH2) is a peptide produced by the prostate gland and then secreted into seminal plasma. Recent studies have shown that the addition of FPP to uncapacitated mouse and human sperm suspensions stimulates capacitation as demonstrated by cytological assessment and increased fertilizing/penetrating ability in vitro, hence its name. Interestingly, the addition of FPP also has an effect on capacitated cells, namely inhibition of spontaneous acrosome loss; these spermatozoa retain high fertilizing ability, however, when tested with unfertilized oocytes. Adenosine, which is known to modulate adenylate cyclase activity, has been shown to elicit responses similar to those obtained with FPP in both uncapacitated and capacitated spermatozoa. Because the use of FPP and adenosine simultaneously is more effective than either used individually, it has been proposed that these two molecules interact with different receptors to modulate the adenylate cyclase/cAMP signal transduction pathway. FPP-related peptides have been found to vary in their biological activity in vitro, the most interesting one being Gln-FPP (pGlu-Gln-ProNH2). This peptide, identified in human seminal plasma and possibly produced by men with prostatic dysfunction, had no intrinsic activity itself but was able to competitively inhibit responses to FPP. Finally, very recent evidence suggests that the protein TCP-11, coded for by a mouse t-complex gene, may be the receptor for FPP. The existence of a human homologue for Tcp-11 suggests that TCP-11 and FPP could well play an important role in human fertility/subfertility. In vitro, FPP's ability to stimulate capacitation might reduce the incidence of delayed fertilization which results in impaired embryonic development and implantation.
Fraser
L R
LR
Anatomy and Human Biology, King's College London, UK.
D000818:Animals; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins / Q000502:physiology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D013075:Sperm Capacitation / Q000502:physiology; D013094:Spermatozoa / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000502:physiology; D044767:Ubiquitin-Protein Ligases; D056427:t-Complex Genome Region
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C533399:TCP11 protein, human; C533400:Tcp11 protein, mouse; D013973:Thyrotropin-Releasing Hormone; C059697:pyroglutamyl-glutamyl-proline amide; C116196:PPP1R11 protein, human; D044767:Ubiquitin-Protein Ligases; D011761:Pyrrolidonecarboxylic Acid