Mutations in the Human Gonadotropin-Releasing Hormone Receptor: Insights into Receptor Biology and Function
Bibliographic record
Abstract
Pulsatile hypothalamic release of GnRH tightly controls reproduction by activating a specific cell membrane receptor (GnRHR) on the surface of pituitary gonadotrophs to stimulate luteinizing hormone and follicle-stimulating hormone secretion. During the last 10 years, 21 loss-of-function GNRHR mutations have been identified in patients with idiopathic hypogonadotropic hypogonadism. Although most patients with hypogonadotropic hypogonadism can be treated by delivery of exogenous pulsatile GnRH, in several cases, patients with GNRHR mutations fail to respond efficiently to GnRH treatment. The impact of each mutation on GnRHR function has been studied extensively in vitro, but correlation with clinical phenotype is not always evident. By combining recent advances into the molecular mechanisms controlling ligand binding and receptor activation with data accumulated from clinical studies, this review summarizes the overall structure-function relationships of the human GnRH receptor, with an emphasis on the impact of naturally occurring mutations. Furthermore, given that it was recently demonstrated that pharmacological chaperones can rescue altered receptor function in vitro, potential therapeutic approaches are also discussed.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
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 source (direct Gemma or distilled Codex), 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".