Cited by 109Ovarian function and disordersSexual Differentiation and DisordersHormonal and reproductive studies

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

Hogeveen, Kevin N., Cousin, Patrice, Pugeat, Michel, Dewailly, Didier, Soudan, Benoît, Hammond, Geoffrey L.·2002·Journal of Clinical Investigation

DOI 10.1172/jci0214060

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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 fail to secrete the predicted truncated form of SHBG. To our knowledge, these are the first examples of human SHBG variants linked to hyperandrogenism and ovarian dysfunction.

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RETRACTED ARTICLE: Development of Electrochemical Immunosensors for Early Diagnosis of Polycystic Ovary Syndrome (PCOS), and Their Potential Mobile Phone Application
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Retracted
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Self-citation

Authors: Hogeveen, K. N., Cousin, P., Pugeat, M., Dewailly, D., Soudan, B., & Hammond, G. L.
Affiliations: Western University (CA)
Inserm (FR)
Centre Hospitalier Universitaire de Lille (FR)
Corresponding author: Hammond, Geoffrey L.
ORCID: Hogeveen, Kevin N.
Dewailly, Didier
Hammond, Geoffrey L.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2002-04-01
Volume: 109
Issue: 7
Pages: 973-981
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci0214060
OpenAlex: W4243534847
Cited by: 107
References: 35
Citations by year: 2026: 3 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 3 · 2019: 4 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 3 · 2014: 4 · 2013: 3 · 2012: 3
FWCI: 7.02
Type: journal article
Language: en
Open access: closed
Locations: Journal of Clinical Investigation (publishedVersion)
Funders: Fondation de France
Canadian Institutes of Health Research
Topics: Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords: sex hormone-binding globulin, hyperandrogenism, polycystic ovary syndrome, ovarian dysfunction, ovarian failure, hirsutism, missense mutations, glycosylation, protein secretion, single nucleotide polymorphisms, frameshift mutation, compound heterozygosity, pregnancy

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

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