Human sex hormone-binding globulin is expressed in testicular germ cells and not in sertoli cells

The human sex hormone-binding globulin (SHBG) gene contains at least two transcription units. A 4.3 kb human SHBG transcription unit encodes the precursor polypeptide, which is processed and secreted by hepatocytes as plasma SHBG. The proximal promoter of this transcription unit differs from the corresponding sequence in other mammals, in which it is also expressed in Sertoli cells. In particular, its proximal promoter sequence contains a binding site for USF transcription factors that represses its activity in Sertoli cells. Although human SHBG is not expressed in Sertoli cells, human SHBG transcripts containing an alternative exon 1 sequence are present in testicular germ cells. These are the products of an -8 kb human SHBG transcription unit, and they appear to encode an SHBG isoform that is 4-5 kDa smaller than plasma SHBG. This sperm SHBG isoform accumulates between the outer acrosomal membrane and the sperm plasma membrane, and it is released during the capacitation reaction. These remarkable differences in human SHBG expression in the testis, when compared to other mammals, force us to reconsider the functional significance of SHBG expression in the testis in relation to male reproduction.