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

Abstract

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 stagedependent 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 multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART)

“…Deletion of the candidate genes, USP9Y and DBY are considered to be responsible for infertility. USP9Y is present as a single copy gene that is expressed in a wide variety of tissues and functions as an ubiquitin hydrolase [47]. DBY encodes an RNA helicase, is ubiquitously expressed and is the major gene located in AZFa region.…”

“…The SHBG expression potentially influences SHBG levels in human sperm and consequently androgen bioavailability. In addition, the fact that SHBG accumulates between the outer acrosomal membrane and the sperm plasma membrane emphasizes the functional significance of SHBG expression in male reproduction [47].…”

Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone–binding globulin gene

“…We first manipulated the diets of mice expressing different human SHBG transgenes (21): one line contains the 4.3-kb transcription unit expressed in liver and kidney (22), while the other contains a larger, 11-kb region of human SHBG that is also expressed in male germ cells (23). When male mice expressing an 11-kb human SHBG transgene were fed a highsucrose diet, human SHBG levels in the blood were reduced by about 50% after 1 week ( Figure 1A).…”

The ATP-binding cassette transporter 1 mediates lipid efflux from Sertoli cells and influences male fertility

“…Germ cells were isolated from the testes of WT mice at 10 weeks of age as described (47,48). Briefly, testes were excised and washed with phosphate buffered saline (PBS) supplemented with penicillin-streptomycin (5 mg/ml), decapsulated, minced for 5 min and incubated in 100 ml of the above PBS solution for 8 min.…”