Bibliographic record
Abstract
The hypothalamic‐pituitary‐adrenal axis (HPA) is regulated by corticotrophin‐releasing hormone (CRH), arginine vasopressin (AVP) and by glucocorticoids. In response to stress, the neuroendocrine system releases CRH and AVP to regulate adrenocorticotropin (ACTH) hormone secretion from the anterior pituitary and glucocorticoids from the adrenal cortex. Increasing levels of circulating glucocorticoids downregulate the synthesis of the glucocorticoid receptor (GR) in various tissues in an endocrine feedback loop and produce inhibitory effects on the secretion of CRH and ACTH (4, to bring back the system to its resting state. Despite this wealth of information, the precise mechanism of feedback regulation remains elusive. We have identified FBR sequences in the human GR gene promoter and examined the roles of GR, CREB and HDAC‐6 in the negative feedback regulation associated with promoter elements of the human GR gene. We have demonstrated that the enhancer and suppression activities contained within the promoter elements of the GR gene occur through the interaction of GR and the active recruitment of HDAC‐6 and phosphorylated CREB (CREB‐P) by the ligand bound GR. We demonstrated a direct involvement between GR, CREB and HDAC‐6 in the feedback regulation. In the cortisol depleted state, phosphorylated CREB binds to the CRE in the composite feedback regulatory element and CBP/p/CAF complexes. This interaction results in the acetylation of core histones and chromatin decondensation which turns the GR gene on. In the presence of active glucocorticoids, nGRE recruits GR‐ligand complexes which tether HDAC‐6 and phosphatase complexes. The GR‐DEX bound HDAC‐6 deacetylates core histones and the GR‐DEX tethered phosphatase dephosphorylates CREB‐P. Deacetylation leads to chromatin condensation and dephosphorylation of CREB‐P which results in its removal from the CRE which turns GR gene off.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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".