The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Human sex hormone-binding globulin variants associated with hyperandrogenism and ovarian dysfunction
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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“Abnormal levels of SHBG and mutations altering the affinity for its ligands are associated with androgen excess and a PCOS phenotype, but have also been implicated in the pathogenesis of cancer and metabolic dysfunction (Hammond, 2016, Hogeveen et al., 2002).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Hogeveen et al., 2002
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Soni, A., Parikh, M., & Gandhi, T. R. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-22300-6.00013-9
Genetic SHBG Deficiency Unmasks the Discrepancy Between Biochemical and Clinical Hypogonadism
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Additional file 1 of Maternal steroid levels and the autistic traits of the mother and infant
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An HMMR-derived SHBG genetic score predicts lower type 2 diabetes risk
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Metadata
- 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.
- Venue
- Journal of Clinical Investigation
- Published
- 2002-04-01
- Volume
- 109
- Issue
- 7
- Pages
- 973-981
- ISSN
- 0021-9738 (ISSN-L)
- 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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