Modulation of mammalian sperm function by fertilization promoting peptide (FPP).

Fertilization promoting peptide (FPP; pGlu-Glu-ProNH2) is produced by the prostate gland and secreted into seminal plasma. When added to uncapacitated mouse and human sperm suspensions, it stimulates capacitation as demonstrated by both cytological changes and increased fertilizing ability in vitro. When added to capacitated suspensions, FPP inhibits spontaneous acrosome loss but cells retain high fertility in vitro. Adenosine elicits similar responses to FPP in both uncapacitated and capacitated cells and FPP + adenosine has a greater effect on uncapacitated cells than either used individually. We have proposed that these two molecules modulate the same pathway (adenylate cyclase/cAMP) but act via different receptors. The structure of FPP is crucial for bioactivity: loss of the terminal amide group abolishes activity and substitution of the central glutamic acid can markedly alter activity. Most recently we have found that stimulation of TCP-11, the product of the mouse t-complex gene Tcp-11, elicits responses indistinguishable from those obtained with FPP and we have hypothesized that the protein TCP-11 is the receptor for FPP. The existence of a human homologue for Tcp-11 suggests that the gene product, in conjunction with FPP, could play an important role in human fertility.