The presence of full-length TU-1A has been demonstrated in human testis, liver, prostate, breast, and brain tissue, in human cancer cell lines derived from prostate and breast, and in the testis of mice containing the 11-kb human SHBG transgene. Exons 1B, 1C, 1D and 1E, have been recently identified and described in human prostate tissue, in LNCaP, PC3, and PZ-HPV7 prostate cancer cell lines, and in several cancer cell lines originating in other tissues. Alternative promoter usage has been shown to enable diversified transcriptional regulation in different cellular conditions or development stages, and along with alternative splicing are the primary sources of 59UTR transcript diversity. Estimates of the number of genes with alternative 59UTRs vary from 12% to 22%, while those of alternative promoter usage range from 10% to 18%. Recent studies have shown that 59UTRs play an important role in regulation of gene expression in a variety of organisms. 59UTRmediated regulation has been shown to modulate gene expression through stimulatory and inhibitory mechanisms, influencing the mRNA secondary structure, mRNA stability and translation efficiency. Specifically, it has been shown that occurrence of start codons and open reading frames upstream of the authentic start codon may affect mRNA translation. The different SHBG 59UTRs exhibit many of the features associated with cellular mRNAs, whose expression is tightly controlled at the level of translation, including uORFs and Vismodegib clinical trial thermodynamically stable predicted RNA structures. The present study determines the impact of exon 1A and 1B 59UTRs on SHBG translation. The SHBG gene is composed of 13 different exons that generate at least 6 different TUs, and a minimum of 19 different transcripts. Each TU is constituted by a common region formed by exons 2 to 8, preceded by one alternative first exon. Only one of the six alternative first exons described presents an ATG in frame with the SHBG coding sequence: TU-1 encodes a leucine-rich signal peptide and is responsible for the production of plasma SHBG by hepatocytes. Translation of TU-1A has been demonstrated in human and mouse sperm containing the 11-kb human SHBG transgene, and it has been suggested that TU-1A translation starts at the first in-frame ATG of exon 2, which encodes methionine 30 of transcripts beginning with exon 1. Translation of TU-1B, -1C, -1D, and -1E has not been previously demonstrated. The presence of TU-1, -1A, -1B, -1C, -1D, and -1E has been shown in human prostate. We previously demonstrated that TU-1B was the most abundant SHBG TU in the LNCaP, PC3, and PZ-HPV7 cell lines, and that transcripts including exon 1 after exon 1A or 1B sequences were also found in prostate cell lines and tissues, indicating that exon 1A/exon 1B.