Expression of ACTH receptor pathway genes in glucose‐dependent insulinotrophic peptide (GIP)‐dependent Cushing's syndrome
Bibliographic record
Abstract
OBJECTIVE: The molecular mechanisms responsible for glucose-dependent insulinotrophic peptide receptor or gastric inhibitory polypeptide receptor (GIPR) ectopic expression and function in GIP-dependent Cushing's syndrome (CS) are still unknown. GIPR presumably acts, like the ACTH receptor (ACTHR), through the Gs protein/cyclic AMP/protein kinase A (PKA) pathway to stimulate steroidogenesis. We studied the expression of several genes involved in this pathway in the adrenal tissues of patients with GIP-dependent CS. DESIGN AND METHODS: RNA was extracted from adrenal tissues from nine patients with GIP-dependent CS [seven ACTH-independent bilateral macronodular adrenal hyperplasia (AIMAH), two adenomas], two control whole adult adrenals, two fasciculata cell-enriched preparations from normal adrenals, seven patients with Cushing's disease (CD) and two normal pancreas. Multiplex reverse transcriptase polymerase chain reaction (RT-PCR) evaluated the expression of GIPR, ACTHR, SF-1, Nur77, DAX-1, CYP11A, 3beta-HSD, CYP21, CREB and CREM genes. RESULTS: GIPR mRNA was overexpressed in all GIP-dependent cases. In normal adrenals and in the adrenal tissues from patients with CD, minimal amounts of GIPR mRNA were detected. ACTHR mRNA expression was observed in all GIP-dependent adrenal tissues. The expression of steroidogenic enzymes and some specific and ubiquitous transcription factors (TFs) involved in the ACTHR cascade was significantly reduced. CONCLUSIONS: Our results indicate that the expression of ACTHR and other genes located downstream in the ACTHR cascade, including steroidogenic enzymes genes and some transcription factors, are relatively suppressed in GIP-dependent CS. Although the expression of aberrant receptors plays an important role in steroidogenesis and initiation of cell proliferation, additional genetic events might occur, altering the activity of the ACTHR pathway.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.002 | 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 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".