Human kallikrein-related peptidase 3 (hK3), also known as prostate-specific 
antigen (PSA), is a 33 kDa single chain glycoprotein belonging to the kallikrein 
family of serine proteases. With chymotrypsin-like enzymatic activity, hK3 is 
directly and indirectly involved in a number of diverse biological functions 
including male fertility, the regulation of cell proliferation, and the 
inhibition of angiogenesis. The gene encoding hK3, hKLK3, is located on 
chromosome 19 and its expression has been shown to be regulated by steroid 
hormones through androgen receptor-mediated transcription. hK3 was once thought 
to be exclusively expressed and secreted by prostatic epithelial cells, hence 
the initial name of prostate-specific antigen, but has since been isolated in 
several nonprostatic tissues and ongoing characterization of alternative 
splicing variants has found at least 13 distinct mRNA transcripts. The detection 
of hK3 in cerebrospinal fluid prompted the hypothesis that hK3 may be produced 
in the brain. To test this notion, in this study we used RT-PCR amplification of 
brain tissue total RNA and examined hK3 protein by immunohistochemical, and 
immunoblot analysis. RT-PCR revealed several hK3 mRNA transcripts in the brain. 
Confirming these findings, both immunohistochemical staining and western 
immunoblotting showed evidence for hK3 protein in neuronal cells. Taken 
together, our findings support the expression of hK3 in neuronal cells 
reinforcing the concept of hK3 as a ubiquitous protein with more multifarious 
biological activity than previously believed. Ongoing research seeks to 
elucidate the functional significance of hK3 in brain cells.