THE ROLE AND REGULATION OF THE NIEMANN-PICK C1 GENE IN ADRENAL STEROIDOGENESIS
Bibliographic record
Abstract
The Niemann-Pick C-1 (NPC-1) gene codes for an intracellular membrane glycoprotein that processes low density lipoprotein (LDL)-imported cholesterol. Its absence is characterized by pathologic accumulation of cholesterol in endosomes and lysosomes. Niemann-Pick C-1 is involved in steroidogenesis in the adrenal, ovary, testis, and placenta. We investigated adrenal morphology of the BALB/c NPC-1(-/-) mutant mouse. Adrenals of mutant and wild type mice were similar at three weeks, but were substantially smaller in NPC-1(-/-) mice at eight weeks. The major histological difference was reduction in the thickness of the zona fasciculata, due to decreased cell volume. Lipid accumulation, revealed by Oil Red-O staining, was restricted to the zona fasciculata in wild type mice, but was found throughout the cortex in NPC-1 mutants. The 5'-flanking region of the mouse NPC-1 gene was cloned and sequenced. Comparison of the proximal promoter region revealed a CpG island and two consensus sequences for the cAMP response element (CRE). The role of the PKA pathway in transactivation of the NPC-1 promoter was probed by transient transfection of a 2.2 kb fragment of the 5'-flanking region fused to the luciferase reporter into mouse adrenal Y-1 and Leydig tumor cells and into nonsteroidogenic monkey kidney CV-1 cells. This promoter fragment displayed significant constitutive transcription, which was enhanced 3-5 fold in steroidogenic cells by treatment with 1 mM cAMP. The cAMP response was muted in CV-1 cells. We conclude that the NPC-1 gene is regulated by cAMP. It plays a role in normal cholesterol homeostasis and is essential for normal adrenal development and function.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".