Human sex hormone-binding globulin variants associated with hyperandrogenism and ovarian dysfunction

The Journal of Clinical Investigation
K N HogeveenG L Hammond

Abstract

The access of testosterone and estradiol to target tissues is regulated by sex hormone-binding globulin (SHBG) in human blood. Serum SHBG levels are low in patients with hyperandrogenism, especially in association with polycystic ovarian syndrome (PCOS) and in individuals at risk for diabetes and heart disease. Here, we identify SHBG coding region variations from a compound heterozygous patient who presented with severe hyperandrogenism during pregnancy. Serum SHBG levels in this patient measured 2 years after her pregnancy were exceptionally low, and her non-protein-bound testosterone concentrations greatly exceeded the normal reference range. A single-nucleotide polymorphism within the proband's maternally derived SHBG allele encodes a missense mutation, P156L, which allows for normal steroid ligand binding but causes abnormal glycosylation and inefficient secretion of SHBG. This polymorphism was identified in four other patients with either PCOS, ioiopathic hirsutism, or ovarian failure. The proband's paternal SHBG allele carries a single-nucleotide deletion within exon 8, producing a reading-frame shift within the codon for E326 and a premature termination codon. CHO cells transfected with a SHBG cDNA carrying this mutation...Continue Reading

References

Oct 16, 1975·Differentiation; Research in Biological Diversity·C Szpirer, J Szpirer
Oct 1, 1992·The Journal of Clinical Endocrinology and Metabolism·S G PowerG L Hammond
Sep 1, 1988·The Journal of Clinical Endocrinology and Metabolism·S R PlymateK E Friedl
Jan 1, 1974·Clinical Endocrinology·D C Anderson
Oct 1, 1984·The Journal of Clinical Endocrinology and Metabolism·W RosnerM S Khan
Aug 14, 1982·Lancet·O D AhrentsenS G Johnsen
Jul 31, 1983·Clinica Chimica Acta; International Journal of Clinical Chemistry·G L Hammond, P L Lähteenmäki
Aug 1, 1981·The Journal of Clinical Endocrinology and Metabolism·M S KhanW Rosner
Jun 1, 1982·The Journal of Clinical Endocrinology and Metabolism·A W Meikle, W M Stanish
Dec 1, 1995·Clinical Obstetrics and Gynecology·H KuhlI Wiegratz
Jan 22, 1998·The Journal of Clinical Endocrinology and Metabolism·P CousinM Pugeat
Jan 24, 1998·Molecular Endocrinology·M JänneG L Hammond
Jan 10, 2002·The Journal of Clinical Investigation·Peter H Byers
Nov 1, 1961·The Journal of Clinical Endocrinology and Metabolism·D FERRIMAN, J D GALLWEY

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