As well as mRNA corresponding to fulllength TU-1A and TU-1B in LNCaP cells and human prostate tissue. With regard to their translation, although we were able to identify the SHBG protein in human prostate, testis and plasma, we could not detect its presence in LNCaP, PC3, and PZ-HPV7 cells or in their supernatant, except when SHBG was overexpressed in LNCaP cells with a Flag-tagged SHBG construct. Moreover, when LNCaP cells were transfected with constructs containing the putative non-coding exons 1A or 1B, the amount of detected SHBG decreased considerably with respect to cells transfected with constructs without these potentially noncoding exons. Importantly, the molecular weight of the detected band did not vary between the 2 groups, suggesting that exons 1A and 1B were acting as 59UTR exons, regulating SHBG translation. These results confirmed that the first in-frame ATG of the exon 2 sequence acts as the first coding codon of TU-1A and TU-1B. In this respect, it has been reported that regulation of translation initiation is a central control point in mammalian cells, and that the rate of initiation limits translation of most mRNAs. Translation regulatory elements in 59UTRs, such as uAUGs, uORFs and complex mRNA MK-2206 secondary structures, are often found in mRNAs encoding regulatory proteins like protooncogenes, growth factors and their receptors, and homeodomain proteins. During embryonic development, the 59UTRs of Antp, Ubx, RARb2, c-mos, and c-myc regulate protein levels in a spatiotemporal manner, and translation initiation of several growth factor mRNAs is specifically regulated during differentiation, growth, and stress. The presence of long 59UTRs containing uAUGs, uORFs, and mRNA secondary structures reduces the efficiency of the scanning process by impeding the ability of ribosomes to interact with the 59UTR in single-stranded form. As SHBG exon 1A and 1B transcripts are poorly translated under normal growth conditions, further experiments should be performed to determine whether, under stress conditions, translation of these transcripts is enhanced. Particularly, in prostate cancer, it would be interesting to determine whether the hypoxia environment and the increased oxidative stress associated to tumor growth favor the translation of these alternative transcripts. Another function of TU-1B might be the regulation of SAT2 gene expression, since it has been described that exon 1B overlaps with the 59UTR sequence of the SAT2 gene, situated on the negative strand of the chromosome 17, and therefore SHBG and SAT2 genes would produce natural sense-antisense pair transcripts that overlap head to head. Regulation of SHBG translation through its 39UTR mRNA sequence by miRNA cannot be ruled out.