Human Types 1 and 3 3α-Hydroxysteroid Dehydrogenases: Differential Lability and Tissue Distribution1
Bibliographic record
Abstract
3 alpha-Hydroxysteroid dehydrogenases (3 alpha-HSDs) catalyze the conversion of 3-ketosteroids to 3 alpha-hydroxy compounds. The best known 3 alpha-HSD activity is the transformation of the most potent natural androgen, dihydrotestosterone, into 5 alpha-androstan-3 alpha,17 beta-diol (3 alpha-diol), a compound having much lower activity. Previous reports show that 3 alpha-HSDs are involved in the metabolism of glucocorticoids, progestins, prostaglandins, bile acid precursors, and xenobiotics. 3 alpha-HSDs could, thus, play a crucial role in the control of a series of active steroid levels in target tissues. In the human, type 1 3 alpha-HSD was first identified as human chlordecone reductase. Recently, we have isolated and characterized type 3 3 alpha-HSD that shares 81.7% identity with human type 1 3 alpha-HSD. The transfection of vectors expressing types 1 and 3 3 alpha-HSD in transformed human embryonic kidney (HEK-293) cells indicates that both enzymes efficiently catalyze the transformation of dihydrotestosterone into 3 alpha-diol in intact cells. However, when the cells are broken, the activity of type 3 3 alpha-HSD is rapidly lost, whereas the type 1 3 alpha-HSD activity remains stable. We have previously found that human type 5 17 beta-HSD which possesses 84% and 86% identity with types 1 and 3 3 alpha-HSD, respectively, is also labile, whereas rodent enzymes such as mouse type 5 17 beta-HSD and rat 3 alpha-HSD are stable after homogenization of the cells. The variable stability of different enzymatic activities in broken cell preparations renders the comparison of different enzymes difficult. RNA expression analysis indicates that human type 1 3 alpha-HSD is expressed exclusively in the liver, whereas type 3 is more widely expressed and is found in the liver, adrenal, testis, brain, prostate, and HaCaT keratinocytes. Based on enzymatic characteristics and sequence homology, it is suggested that type 1 3 alpha-HSD is an ortholog of rat 3 alpha-HSD while type 3 3 alpha-HSD, which must have diverged recently, seems unique to human and is probably more involved in intracrine activity.
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".