A Human Sex Hormone-binding Globulin Isoform Accumulates in the Acrosome during Spermatogenesis

Human sex hormone-binding globulin (SHBG) binds estradiol and testosterone with high affinity. Plasma SHBG is produced by hepatocytes, but the human SHBG gene is also expressed in the testis. Little is known about SHBG gene expression in the human testis, but human SHBG transcripts accumulate in a spermatogenic stage-dependent manner in the testes of mice containing an 11-kb human SHBG transgene. We have now found that human SHBG transcripts containing an alternative exon 1 sequence are located specifically in the testicular germ cells of these transgenic mice, whereas murine SHBG transcripts are confined to Sertoli cells. In addition, we have detected immunoreactive human SHBG in the acrosome during all stages of spermiogenesis in mice containing an 11-kb human SHBGtransgene. Western blots of germ cell extracts from these transgenic mice and from human sperm indicate that the immunoreactive human SHBG in the acrosome composes electrophoretic variants, which are 3–5 kDa smaller than the major electrophoretic isoforms of human SHBG in the blood. This apparent size difference is due in part to differences in glycosylation of plasma and acrosomal SHBG isoforms. The function of the human SHBG isoform in the acrosome is unknown, but it binds steroid ligands with high affinity. This is the first demonstration that humanSHBG transcripts encode an SHBG isoform that remains within a cellular compartment. Human sex hormone-binding globulin (SHBG) binds estradiol and testosterone with high affinity. Plasma SHBG is produced by hepatocytes, but the human SHBG gene is also expressed in the testis. Little is known about SHBG gene expression in the human testis, but human SHBG transcripts accumulate in a spermatogenic stage-dependent manner in the testes of mice containing an 11-kb human SHBG transgene. We have now found that human SHBG transcripts containing an alternative exon 1 sequence are located specifically in the testicular germ cells of these transgenic mice, whereas murine SHBG transcripts are confined to Sertoli cells. In addition, we have detected immunoreactive human SHBG in the acrosome during all stages of spermiogenesis in mice containing an 11-kb human SHBGtransgene. Western blots of germ cell extracts from these transgenic mice and from human sperm indicate that the immunoreactive human SHBG in the acrosome composes electrophoretic variants, which are 3–5 kDa smaller than the major electrophoretic isoforms of human SHBG in the blood. This apparent size difference is due in part to differences in glycosylation of plasma and acrosomal SHBG isoforms. The function of the human SHBG isoform in the acrosome is unknown, but it binds steroid ligands with high affinity. This is the first demonstration that humanSHBG transcripts encode an SHBG isoform that remains within a cellular compartment. Mammalian genes encoding sex hormone-binding globulin (SHBG) 1The abbreviations used are: SHBG, sex hormone-binding globulin; ABP, androgen-binding protein; DHT, 5α-dihydrotestosterone; PBS, phosphate buffered saline; WT, wild type; RT, reverse transcription; DCC, dextran-coated charcoal. contain at least two transcription units (1Hammond G.L. Underhill D.A. Rykse H.M. Smith C.L. Mol. Endocrinol. 1989; 3: 1869-1876Google Scholar, 2Joseph D.R. Vitam. Horm. 1994; 49: 197-280Google Scholar). In humans, the transcription unit responsible for the production of plasma SHBG by hepatocytes consists of eight exons that span ∼3.2 kb on chromosome 17 (1, 3) and is under the control of a promoter sequence that contains several well defined binding sites for liver-enriched transcription factors (4Jänne M. Hammond G.L. J. Biol. Chem. 1998; 273: 34105-34114Google Scholar, 5Hogeveen K.N. Talikka M. Hammond G.L. J. Biol. Chem. 2001; 276: 36383-36390Google Scholar). The human SHBG gene contains a second transcription unit that consists of an alternative exon 1 sequence that replaces the exon 1 sequence present in the SHBG mRNA found in the liver. As a consequence, these differentially spliced SHBG transcripts lack the secretion signal sequence associated with the plasma SHBG precursor polypeptide. The expression of the SHBG gene in the testis has been studied extensively in the rat (2Joseph D.R. Vitam. Horm. 1994; 49: 197-280Google Scholar). In this species, theSHBG gene is expressed in Sertoli cells (6Reventos J. Hammond G.L. Crozat A. Brooks D.E. Gunsalus G.L. Bardin C.W. Musto N.A. Mol. Endocrinol. 1988; 2: 125-132Google Scholar, 7Hall S.H. Conti M. French F.S. Joseph D.R. Mol. Endocrinol. 1990; 4: 349-355Google Scholar) and encodes the SHBG homologue that is generally known as the testicular androgen-binding protein (ABP). The ABP produced by rat Sertoli cells is secreted into the lumen of seminiferous tubules where it is thought to serve primarily as a carrier of testosterone throughout the male reproductive tract (2Joseph D.R. Vitam. Horm. 1994; 49: 197-280Google Scholar). Although SHBG transcripts are present in the human testis (1Hammond G.L. Underhill D.A. Rykse H.M. Smith C.L. Mol. Endocrinol. 1989; 3: 1869-1876Google Scholar), virtually nothing is known about their function or how they are regulated, and evidence that they encode a precursor polypeptide containing a leader sequence for secretion is lacking. In fact, all the available evidence suggests that the human testis contains several alternative SHBG transcripts comprising a non-coding alternative exon 1 sequence and some of them also lack exon 7 sequences (1Hammond G.L. Underhill D.A. Rykse H.M. Smith C.L. Mol. Endocrinol. 1989; 3: 1869-1876Google Scholar, 8Gershagen S. Lundwall A. Fernlund P. Nucleic Acids Res. 1989; 17: 9245-9258Google Scholar). Differentially spliced humanSHBG transcripts lacking exon 7 sequences have also been identified in several other tissues (9Misao R. Nakanishi Y. Fujimoto J. Tamaya T. Cancer Res. 1997; 57: 5579-5583Google Scholar, 10Misao R. Nakanishi Y. Fujimoto J. Tamaya T. Fertil. Steril. 1998; 69: 324-328Google Scholar), but their 5′-sequences have not been characterized. Like the human SHBG gene, the rat SHBG gene produces transcripts that consist of alternative exon 1 sequences, and these have been identified in the rat brain (11Wang Y.-M. Bayliss D.A. Millhorn D.E. Petrusz P. Joseph D.R. Endocrinology. 1990; 127: 3124-3130Google Scholar) and the fetal rat liver (12Sullivan P.M. Wang Y.-M. Joseph D.R. Mol. Endocrinol. 1993; 7: 702-715Google Scholar). There is no obvious sequence similarity between the alternative exon 1 sequences associated with various SHBG transcripts in different species, but there is evidence they encode SHBG isoforms comprising subcellular localization signals within a unique amino-terminal sequence (13Joseph D.R. Becchis M. Fenstermacher D.A. Petrusz P. Endocrinology. 1996; 137: 1138-1143Google Scholar). To study the tissue-specific expression of various humanSHBG transcripts, we have produced several lines of transgenic mice (14Jänne M. Deol H.K. Power S.G.A. Yee S.-P. Hammond G.L. Mol. Endocrinol. 1998; 12: 123-136Google Scholar) containing either a 4- or an 11-kb humanSHBG transgene. The 4-kb transgene consists of the eight exons encoding plasma SHBG (1Hammond G.L. Underhill D.A. Rykse H.M. Smith C.L. Mol. Endocrinol. 1989; 3: 1869-1876Google Scholar) and 0.9 kb of 5′-flanking DNA that includes the promoter utilized in the liver (4Jänne M. Hammond G.L. J. Biol. Chem. 1998; 273: 34105-34114Google Scholar), whereas the 11-kb human SHBG transgene contains an additional 5′-flanking DNA sequence that includes an alternative exon 1 sequence associated with the SHBG transcripts present in the human testis (1Hammond G.L. Underhill D.A. Rykse H.M. Smith C.L. Mol. Endocrinol. 1989; 3: 1869-1876Google Scholar, 8Gershagen S. Lundwall A. Fernlund P. Nucleic Acids Res. 1989; 17: 9245-9258Google Scholar). We have shown previously that only the 11-kb human SHBGtransgene is expressed in the mouse testis, as evidenced by the presence of human SHBG transcripts in the seminiferous epithelium (14Jänne M. Deol H.K. Power S.G.A. Yee S.-P. Hammond G.L. Mol. Endocrinol. 1998; 12: 123-136Google Scholar). These studies also indicated that the humanSHBG transcripts accumulate in a spermatogenic cycle stage-dependent manner in this location, but the cell type in which they were located could not be clearly identified, and their protein products eluded detection (14Jänne M. Deol H.K. Power S.G.A. Yee S.-P. Hammond G.L. Mol. Endocrinol. 1998; 12: 123-136Google Scholar). We have therefore re-examined this issue, and we have found that the majority of humanSHBG transcripts in the testis of these mice consist of the alternative exon 1 sequence associated with SHBG cDNAs from a human testis library (1Hammond G.L. Underhill D.A. Rykse H.M. Smith C.L. Mol. Endocrinol. 1989; 3: 1869-1876Google Scholar). Furthermore, these alternatively spliced humanSHBG transcripts are confined to testicular germ cells and an immunoreactive human SHBG isoform accumulates in the acrosome of developing spermatids and immature sperm in the transgenic mice. We have also obtained direct evidence that this acrosomal SHBG isoform binds steroids and is also present in human sperm. Transgenic mice containing 11-kb (linesshbg 11-a and shbg 11-b) or 4-kb (linesshbg 4-a and shbg of humanSHBG gene have been previously (14Jänne M. Deol H.K. Power S.G.A. Yee S.-P. Hammond G.L. Mol. Endocrinol. 1998; 12: 123-136Google Scholar, M. K.N. Deol H.K. Hammond G.L. Endocrinology. Scholar). were under and with and of mice were for the of Sertoli cells germ cells for protein and mice were with by (14Jänne M. Deol H.K. Power S.G.A. Yee S.-P. Hammond G.L. Mol. Endocrinol. 1998; 12: 123-136Google Scholar). were by the of the on of Western The SHBG for were from a by to human SHBG Hammond G.L. J. Biol. Chem. Scholar), to from mice were in at for with a of and in The were and at high in a for in The were at for and with a for 7 to at with human The immunoreactive human SHBG detected the from from transgenic mice (14Jänne M. Deol H.K. Power S.G.A. Yee S.-P. Hammond G.L. Mol. Endocrinol. 1998; 12: 123-136Google Scholar) were on for in and with in for at the were with for 7 at The were with the human SHBG at and detected the of Sertoli cells and germ cells from the testes of and transgenic mice M. M. P. Biol. 1997; 57: Scholar). the testes were and in with and M. M. P. Biol. 1997; 57: Scholar). The testes were and in a at for with the were in of the and to for This second with at for the were with and for and protein cells were from the mouse testes an M. M. P. Biol. 1997; 57: Scholar). testes were and with with and M. M. P. Biol. 1997; 57: Scholar), and for in the The and the testicular were in containing at for The by and the with at for The tubules were to several of and as previously M. M. P. Biol. 1997; 57: Scholar, J. Endocrinology. Scholar). the in of with fetal and in a for The containing germ cells Sertoli cells and two with PBS, the in for protein or protein from of Sertoli cells and germ cells and from germ cells with at for Human sperm were for to plasma and and sperm were either in or by to with by in a and were in and to with and in the and in the were T. J. S. A. Scholar) to The were first for 1 in containing and and were at with human SHBG by in the The blots were in containing for to and were identified a and by to To the of glycosylation on the electrophoretic of immunoreactive human SHBG in different and protein extracts from testicular we a Western this protein from testicular cells with by in a and and cell by were at as by the to by and Western as from mouse testicular cells and liver by on a in the presence of and to a The with various human SHBG the exons G.L. Underhill D.A. Smith C.L. Musto N.A. Bardin C.W. Scholar), the SHBG exon 1 sequence encoding the leader sequence for secretion of SHBG, and the exon 1 sequence (1Hammond G.L. Underhill D.A. Rykse H.M. Smith C.L. Mol. Endocrinol. 1989; 3: 1869-1876Google Scholar). In addition, cDNAs for mouse and protein 1 were used as for cells and germ In some a mouse SHBG to exon sequences used as a and a for also used as an additional control for and M. K.N. Deol H.K. Hammond G.L. Endocrinology. Scholar). We also used the from germ cells to the human SHBG To reverse transcription at for of and units of with an and by of the in a in the presence of 1 unit of of and of this we used an to a in the SHBG alternative exon 1 and a reverse to a sequence within exon of the human SHBG gene (1Hammond G.L. Underhill D.A. Rykse H.M. Smith C.L. Mol. Endocrinol. 1989; 3: 1869-1876Google Scholar). The for at for for and for 1 mouse protein 1 by under the as two and to control for the and of germ cell mRNA in the The products were by in a and the were the and containing products were To the immunoreactive SHBG from testicular cells binds we used a binding on Endocrinology. Scholar). In this the steroids were first from protein extracts by in a dextran-coated and for at to the DCC, of the were and at for 1 with by an additional at binding in the presence of by with an and of the by the containing for G.L. Scholar). used to the of the immunoreactive SHBG from the acrosome and a Y. Scholar) to the and a binding to as previously G.L. Scholar). used to the of human SHBG transcripts in of Sertoli cells and germ as well as a of germ cells from the testes of mice and mice containing 4- or 11-kb human SHBG a human SHBG that exon sequences used as human were only detected in extracts of testicular cells from mice containing the 11-kb human SHBG transgene. The of mouse of and protein 1 germ cell cDNAs to the of the germ cells from the testes of transgenic mice 7 and These indicate that of germ cells were present in all as evidenced by the presence of of protein 1 the of human in the germ to that in the of Sertoli cells and germ this that the SHBG transcripts in the testis of 11-kb humanSHBG transgenic mice be from Sertoli cells. To the human SHBG transcripts that accumulate in testicular germ a of extracts of germ from transgenic mice containing either the 4- or 11-kb human SHBG exon and alternative exon As a we also a of from an 11-kb humanSHBG transgenic mouse liver the of signals obtained these exon cDNAs with obtained a to human SHBG exon sequences it is apparent that are only present in germ cells from the 11-kb humanSHBG transgenic mice. As the in the liver the exon 1 sequence containing the for the SHBG precursor polypeptide and the leader sequence for the SHBG in the germ cells from mice containing the 11-kb human SHBG transgene only be detected the cDNAs that the alternative exon 1 sequence and sequences to exons The human alternative SHBG transcripts were also in germ cells from transgenic mice by an with for human SHBG alternative exon 1 and human and mouse protein were used in an as a control for the presence of mRNA Human SHBG transcripts were detected only in the cells of the 11-kb human SHBG transgenic mice, whereas mouse protein 1 in all from 4-kb human SHBG transgenic mice and mice the two products human were and the 3) found to contain the alternative exon 1 sequence by the sequences of exons whereas the smaller and the alternative exon 1 sequence by the sequences of exons and of the mouse SHBG gene in the testicular cell from mice by and mouse and protein 1 cDNAs were used to for the presence of cells and germ we used a to mouse SHBG exon sequences, murine SHBG transcripts were only detected in the of Sertoli cells and germ cells. Although of protein 1 mRNA were detected in the two different testicular cell murine SHBG transcripts could not be detected in the germ cells These therefore indicate that the mouse SHBG gene is expressed in Sertoli cells than in germ cells. The human SHBG not in the testes of mice, and this the of the at in the of testes from transgenic mice containing the 4- or 11-kb human In these of immunoreactive human SHBG are present in the of transgenic mouse of the size of the human SHBG transgene. we have been to human SHBG transcripts in the testes of mice containing the 4-kb human SHBG and the plasma of human SHBG are in these two lines of transgenic mice (14Jänne M. Deol H.K. Power S.G.A. Yee S.-P. Hammond G.L. Mol. Endocrinol. 1998; 12: 123-136Google Scholar), the in the the of SHBG from the In to studies (14Jänne M. Deol H.K. Power S.G.A. Yee S.-P. Hammond G.L. Mol. Endocrinol. 1998; 12: 123-136Google Scholar), in which we were not to immunoreactive human SHBG within the seminiferous tubules of mice containing human SHBG of in a high human SHBG within the seminiferous tubules of the 11-kb human SHBG transgenic mouse testis this immunoreactive human SHBG could be detected within the acrosome of spermatids during spermiogenesis only in the seminiferous tubules of transgenic mice containing the 11-kb human SHBG transgene this could be detected in the acrosome as as it to on spermatids of and in the acrosome as it throughout the stages of spermiogenesis To the immunoreactive human SHBG remains within the acrosome sperm are into the male reproductive we on sperm from the of transgenic mice containing either the 4- or 11-kb human and this clearly that immunoreactive human SHBG is only present in the acrosome of sperm from the 11-kb human SHBG transgenic mice To the size of the immunoreactive SHBG within the acrosome of 11-kb human SHBG transgenic mouse germ we used Western to protein extracts from testicular a of Sertoli cells and germ cells or germ cells. The lack of immunoreactive in the protein of testicular cells from mice the of the SHBG used for this In addition, there no in the protein of testicular cells from mice containing a 4-kb human SHBG transgene the that the testes of these contain of in the cell the immunoreactive protein in the testicular cell extracts of mice containing the 11-kb transgene be for by of SHBG from or the cell compartment. In Western of the testicular protein we that the apparent size of the immunoreactive human SHBG in these smaller than that in a from the and that electrophoretic different from that associated with human SHBG from To this we the electrophoretic of immunoreactive SHBG in and testicular cell extracts from the 11-kb human mice. this of the were also with to to Western This that the apparent size of immunoreactive human SHBG in the testicular protein is smaller and than the major electrophoretic isoform of SHBG in with clearly the electrophoretic of immunoreactive SHBG in and in immunoreactive products of about kDa for SHBG and kDa for acrosomal SHBG The of the immunoreactive human SHBG in the protein extracts from testicular cells were also a indicated that binding could only be detected in the extracts from mice containing the 11-kb human SHBG transgene and that the were present in of these mice (14Jänne M. Deol H.K. Power S.G.A. Yee S.-P. Hammond G.L. Mol. Endocrinol. 1998; 12: 123-136Google Scholar). We therefore protein extracts of of Sertoli cells and germ cells from these mice to study the steroid binding of the SHBG from the as that the of the acrosomal SHBG is the as SHBG in Furthermore, a with other SHBG ligands that testosterone and estradiol as for the binding of to the acrosomal SHBG, as with SHBG of the binding of steroid ligands for and acrosomal SHBG binding as a of the of steroid in in binding of to the of to the by as a of the of steroid in in binding of to the of to the by in a that expression of alternative humanSHBG transcripts in the testis of transgenic mice in of an SHBG isoform in the acrosome of sperm to SHBG is also present in human sperm. To we the electrophoretic of human SHBG in a with human SHBG in sperm in and sperm that been by This Western that the apparent size of the immunoreactive SHBG in human sperm is about kDa smaller than SHBG in either or Furthermore, of immunoreactive SHBG in human sperm is to that of the immunoreactive SHBG from the testicular cells of 11-kb human SHBG transgenic mice but is with to electrophoretic on studies of ABP production by the rat testis (2Joseph D.R. Vitam. Horm. 1994; 49: 197-280Google Scholar), it is generally that the presence of an protein in the of other is the gene expression in Sertoli cells on Endocrinology. Scholar). In the transcription unit responsible for plasma SHBG production by the fetal liver is also expressed in the testis of (2Joseph D.R. Vitam. Horm. 1994; 49: 197-280Google Scholar), with the of expression in Sertoli cells during (6Reventos J. Hammond G.L. Crozat A. Brooks D.E. Gunsalus G.L. Bardin C.W. Musto N.A. Mol. Endocrinol. 1988; 2: 125-132Google Scholar, D.R. S.H. French F.S. S. A. Scholar). In the 4-kb human unit that is expressed in the liver of transgenic mice is not expressed in the testis (14Jänne M. Deol H.K. Power S.G.A. Yee S.-P. Hammond G.L. Mol. Endocrinol. 1998; 12: 123-136Google Scholar), the that the rat SHBG transcription unit with a is expressed as a transgene in the mouse testis J. P.M. Joseph D.R. Mol. Endocrinol. 1993; Scholar). These an that there are differences in the the SHBG gene is expressed in the testis. this they clearly that the human and SHBG genes are expressed in different cell within the testis. Like the expression of the gene to be confined to Sertoli cells. expression of human SHBG in the mouse testis in germ and the transcripts consist of an alternative exon 1 sequence to that present in several SHBG cDNAs from a human testis library (1Hammond G.L. Underhill D.A. Rykse H.M. Smith C.L. Mol. Endocrinol. 1989; 3: 1869-1876Google Scholar). cell differences in SHBG expression in the testis of different is due to the of different transcription units under the control of promoter In the germ the human SHBG gene to be under the control of a promoter the alternative exon 1 M. and and 4-kb humanSHBG are not expressed in the mouse testis they lack this alternative exon 1 and nothing is known about how this promoter is but studies (14Jänne M. Deol H.K. Power S.G.A. Yee S.-P. Hammond G.L. Mol. Endocrinol. 1998; 12: 123-136Google Scholar) have shown that humanSHBG transcripts within the seminiferous epithelium of transgenic mice to in at of and the are found between stages and This well with the at which the R. and of the Scholar) and we first immunoreactive human SHBG in the germ cells. The of germ cells as the cell type in which the alternative are located now to an cell type for studies of how the promoter that their expression is Differentially spliced SHBG transcripts have been identified in several human and in these transcripts lack exon 7 sequences (1Hammond G.L. Underhill D.A. Rykse H.M. Smith C.L. Mol. Endocrinol. 1989; 3: 1869-1876Google Scholar, R. Nakanishi Y. Fujimoto J. Tamaya T. Cancer Res. 1997; 57: 5579-5583Google Scholar, 10Misao R. Nakanishi Y. Fujimoto J. Tamaya T. Fertil. Steril. 1998; 69: 324-328Google Scholar). of human SHBG transcripts in the germ cells of transgenic mice by also indicate that some alternative exon 1 containing human SHBG transcripts lack exon 7 This type of alternatively spliced in a of the encoding an SHBG and this type of and as shown K.N. P. M. Hammond G.L. J. Scholar) for a human SHBG by an with a in exon In addition, human SHBG transcripts lacking exon 7 sequences a of SHBG, this protein lack sites and Western that the immunoreactive human SHBG in the mouse germ cells We therefore that the human SHBG isoform we have identified in the acrosome be the of a lacking exon also indicate that the human in the mouse germ cells consists of the alternative exon 1 sequence by a sequence to human (1Hammond G.L. Underhill D.A. Rykse H.M. Smith C.L. Mol. Endocrinol. 1989; 3: 1869-1876Google Scholar). The of this alternative exon 1 sequence has not been identified, but and with the humanSHBG sequence (1Hammond G.L. Underhill D.A. Rykse H.M. Smith C.L. Mol. Endocrinol. 1989; 3: 1869-1876Google Scholar) indicate that the alternative exon 1 sequence an This that the first is the for in the SHBG protein which is located in exon (1Hammond G.L. Underhill D.A. Rykse H.M. Smith C.L. Mol. Endocrinol. 1989; 3: 1869-1876Google Scholar). the size of the acrosomal SHBG isoform is within kDa of the size of SHBG in the it is that to in SHBG the acrosomal SHBG isoform be at least kDa smaller than the Furthermore, the acrosomal SHBG isoform accumulates in the which from that from the and it therefore consist of a leader sequence that is as the protein the we that of the major alternative human SHBG in testicular germ cells from a as part of an S. S. 2001; Scholar) and that the precursor polypeptide it encodes a amino-terminal leader The electrophoretic of acrosomal SHBG is than SHBG in by and indicate that this is due to a difference in the This also be to the that spermatids at all stages of were used for the of acrosomal SHBG, and the that the of in the acrosome throughout spermiogenesis in a manner J. M. Scholar). Although the of within the of SHBG remains it has been shown previously S. Hammond G.L. Endocrinology. Scholar) that the glycosylation has no on steroid binding is a of and is to be G.L. in at Scholar). could for the of SHBG to with other on the of cell 1988; Scholar), and this be to function in the the differences in the testes of and and the that lack SHBG in the it is not that there are differences in the the human and genes are expressed in the testis. studies have shown that the of a rat SHBG transgene in the Sertoli cells of the mouse testis in an in germ cell J. Endocrinology. Scholar), but this not in 11-kb humanSHBG transgenic mice in which the transgene is expressed within the germ cells. Furthermore, there are differences in the of SHBG gene expression in the testis of mice and Y.-M. P.M. Petrusz P. Joseph D.R. Mol. Endocrinol. 1989; Scholar), and to that human Sertoli cells a protein with to SHBG have not been P. S. M. T. A. J. Mol. Biol. Scholar). In this there is also no to that SHBG gene products function in the human and testis. on the that human SHBG accumulates in the acrosome of sperm in transgenic mice, we human sperm and that an SHBG which be from plasma SHBG on the of electrophoretic is also present in human sperm. The SHBG from human sperm is smaller and than that from transgenic mouse testicular and this be due to glycosylation of the SHBG in human sperm with the SHBG from of germ cells at different stages of J. M. Scholar). These to that the expression of the human SHBG transgene in mice the in the human testis and that production of an SHBG isoform in germ cells also in in the acrosome of human sperm. mice the 11-kb human SHBG transgene in their testes are (14Jänne M. Deol H.K. Power S.G.A. Yee S.-P. Hammond G.L. Mol. Endocrinol. 1998; 12: 123-136Google Scholar), and this suggests the presence of human SHBG in the acrosome has no on sperm function in this that it have on either sperm or for be to in these also not be to the human of differences in sperm and human SHBG accumulate in the acrosome therefore remains to be and of the of SHBG in various and human sperm some on In this the that acrosomal SHBG the to steroids is of and the of steroid ligands are to human SHBG in this in to about human SHBG gene expression in the testis, studies the first evidence that human SHBG transcripts encode an SHBG isoform that is from plasma SHBG, and which serve a function to steroid We Power for for for the human SHBG, and and for

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