Human Sperm Sex Hormone-Binding Globulin Isoform: Characterization and Measurement by Time-Resolved Fluorescence Immunoassay

Abstract

Abstract Context: SHBG gene expression in human testis results in an SHBG isoform that accumulates in the sperm head. Objective: The objective of this study was to further characterize the SHBG isoform in human sperm and to assess its biological relevance. Design, Setting, and Patients: A time-resolved immunofluorometric assay was established to measure SHBG isoform concentrations in sperm samples from patients and sperm donors attending in vitro fertilization clinics. Results and Conclusions: Molecular characterization of SHBG transcripts in human testis and sperm and biochemical analyses of the sperm SHBG isoform indicate that its smaller size compared with plasma SHBG is due to a lack of amino-terminal residues. The SHBG isoform is lost from sperm by one freeze and thaw cycle and during capacitation, which suggests it is located in or between the outer acrosomal and sperm plasma membranes. Sperm SHBG levels were proportional to the number of sperm analyzed and within assay variability in samples taken on different occasions from seven of nine individuals. Intra- and interassay variability (coefficient of variation) was 5.8 and 8.5%, respectively. Sperm SHBG levels ranged from 6–49 pm/106 sperm in 13 donor samples and did not correlate with serum SHBG levels. Sperm SHBG levels were lowest in fertile men and highest in patients with untreated varicocele, but these differences were not significant. Patients studied for couple infertility and those with surgically treated varicocele showed intermediate values. Sperm SHBG isoform levels correlate significantly with age and sperm motility and may influence sperm function in relation to male fertility.