Human sex hormone–binding globulin variants associated with hyperandrogenism and ovarian dysfunction
Bibliographic record
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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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".