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J. Biol. Chem., Vol. 277, Issue 47, 45291-45298, November 22, 2002
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From the Departments of Obstetrics & Gynecology and Pharmacology & Toxicology, and the Canadian Institutes of Health Research Group in
Fetal and Neonatal Health and Development, University of Western
Ontario, London, Ontario N6A 4L6, Canada
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 SHBG
transgene. 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 human
SHBG transcripts encode an SHBG isoform that remains within
a cellular compartment.
A Human Sex Hormone-binding Globulin Isoform Accumulates in the
Acrosome during Spermatogenesis*
,
*
This work was supported in part by a grant from the Canadian
Institutes of Health Research.The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Recipient of a Canadian Institutes of Health Research studentship.
§
Holds the Ivey Chair in Environmental Toxicology. To whom
correspondence should be addressed: London Regional Cancer Centre, 790 Commissioners Rd. East, London, Ontario N6A 4L6, Canada. Tel.: 519-685-8637; Fax: 519-685-8616; E-mail: ghammond@uwo.ca.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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