The role of FSH in castration-induced adipogenesis: Highlighting differences between orchiectomy, GNRH agonists, and antagonists.
Bibliographic record
Abstract
e16011 Background: Androgen deprivation therapy (ADT) results in weight gain and development of the metabolic syndrome. Inspired by the observation that adiposity accompanies the incremental increase in serum FSH levels in menopause, we hypothesized that GNRH antagonist which lower FSH levels will associate with reduced adiposity as compared to GNRH analogues and orchiectomy. Methods: 3T3-L1 fibroblasts differentiation into adipocytes and intracellular lipid accumulation were examined in the presence of escalating FSH doses (0-1000 IU/L) in charcoal stripped FCS supplemented medium to simulate castration. Cellular lipogenesis was assessed by image analysis (oil red staining) and by immunoblotting for fatty acid synthase (FAS) expression. In vivo, 6-week old C57Bl/6 male mice (n=30) were divided to receive either: orchiectomy + vehicle, sham procedure + vehicle, orchiectomy + GNRH antagonist (degarelix 50 mg/kg in vehicle), sham + degarelix, orchiectomy + GNRH analogue (enantone 2 mg/kg in vehicle), or sham + enantone. Serum testosterone, LH and FSH levels and differences in animal weight, visceral fat mass (VFm) and liver lipogenesis (oil red staining) were determined following sacrifice at 6 weeks. BMI was measured as weight (gr) divided by the distance between the tail root and the lower incisors (cm2). Results: The mean lowest and highest serum FSH levels were recorded in mice treated with Degarelix vs. orchiectomy (0.43 and 0.935 mIU/mL resp,) and the mean lowest and highest serum testosterone levels were in mice treated with orchiectomy+degarelix vs. sham control (0.12 and 13.1 ng/ml resp). Mice treated with degarelix had a significantly lower BMI compared to enantone (p=0.02). VFm (perirenal fat weight) was significantly lower (p=0.035) in mice castrated by degarelix (mean 0.38gr) as compared to enantone(mean 0.47gr)). Addition of degarelix or enanton to orchiectomy increased the differences in VFm and BMI between the two groups (0.12gr vs. 0.47gr and 3.73 vs. 4.29 gr/cm2 resp.) In vitro, FSH increased lipid accumulation and FAS expression in 3T3-L1 cells. Conclusions: FSH level elevation following castration promotes fat accumulation and weight gain in preclinical models.
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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".