MODULATION OF MAMMALIAN SPERM FUNCTION BY FERTILIZATION PROMOTING PEPTIDE (FPP)

Fertilization promoting peptide (FPP; pGlu-Glu-PronNH(2)) is produced by the prostate gland and secreted into seminal plasma. When added to uncapacitated mouse and human sperm suspensions, it stimulates capacit ation as demonstrated by both cytological changes and increased fertil izing ability in vitro. When added to capacitated suspensions, FPP inh ibits spontaneous acrosome loss but cells retain high fertility in vit ro. Adenosine elicits similar responses to FPP in both uncapacitated a nd capacitated cells and FPP+ adenosine has a greater effect on uncapa citated cells than either used individually. We have proposed that the se two molecules modulate the same pathway (adenylate cyclase/cAMP) bu t act via different receptors. The structure of FPP is crucial for bio activity: loss of the terminal amide group abolishes activity and subs titution of the central glutamic acid can markedly alter activity. Mos t recently we have found that stimulation of TCP-11, the product of th e mouse t-complex gene Tcp-11, elicits responses indistinguishable fro m those obtained with FPP and we have hypothesized that the protein TC P-11 is the receptor for FPP. The existence of a human homologue for T cp-11 suggests that the gene product, in conjunction with FPP, could p lay an important role in human fertility.