Ectopic and Abnormal Hormone Receptors in Adrenal Cushing’s Syndrome*
Why this work is in the frame
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Bibliographic record
Abstract
The mechanism by which cortisol is produced in adrenal Cushing's syndrome, when ACTH is suppressed, was previously unknown and was referred to as being "autonomous." More recently, several investigators have shown that some cortisol and other steroid-producing adrenal tumors or hyperplasias are under the control of ectopic (or aberrant, illicit, inappropriate) membrane hormone receptors. These include ectopic receptors for gastric inhibitory polypeptide (GIP), -adrenergic agonists, or LH/hCG; a similar outcome can result from altered activity of eutopic receptors, such as those for vasopressin (V1-AVPR), serotonin (5-HT 4 ), or possibly leptin. The presence of aberrant receptors places adrenal cells under stimulation by a trophic factor not negatively regulated by glucocorticoids, leading to in-creased steroidogenesis and possibly to the proliferative phenotype. The molecular mechanisms responsible for the abnormal expression and function of membrane hormone receptors are still largely unknown. Identification of the presence of these illicit receptors can eventually lead to new pharmacological therapies as alternatives to adrenalectomy, now demonstrated by the long-term control of ectopic -ARand LH/hCGR-dependent Cushing's syndrome by propanolol and leuprolide acetate. Further studies will potentially identify a larger diversity of hormone receptors capable of coupling to G proteins, adenylyl cyclase, and steroidogenesis in functional adrenal tumors and probably in other endocrine and nonendocrine tumors. (Endocrine Reviews 22: 75-110, 2001) I. Introduction II. Hormonal Regulation of the Normal Adrenal Cortex III. Primary Adrenal Cushing's Syndrome (CS) IV. Initial in Vitro Evidence of Ectopic Adrenal Membrane Hormone Receptors V. In Vivo Demonstration of the Functionality of Ectopic or Abnormal Membrane Hormone Receptors A. Food-and GIP-dependent CS B. Vasopressin-responsive CS C. Catecholamine-dependent CS D. LH-dependent CS E. LH-dependent adrenal androgen-secreting tumors F. Serotonin-responsive CS G. Steroid-responsive CS H. Other abnormal hormone responses in adrenal CS VI. Investigation Strategy A. Initial clinical screening protocol B. Further characterization of abnormal hormone receptors C. Systematic clinical screening for ectopic/abnormal hormone receptors VII. Molecular Mechanisms of Ectopic/Abnormal Hormone Receptors A. Tissue-specific expression and regulation of membrane hormone receptors B. Potential mechanisms of ectopic or abnormal hormone receptors C. Role of ectopic hormone receptors in adrenocortical cell proliferation VIII. Ectopic/Abnormal
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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 | 0.000 | 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 | 0.000 | 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 it