The role of FSH in castration-induced adipogenesis and cardiovascular diseases: Highlighting differences between orchiectomy, GNRH agonists, and antagonists.
Bibliographic record
Abstract
191 Background: Androgen deprivation therapy (ADT) is associated with weight gain and development of the metabolic syndrome (MS). Different modes of ADT can achieve castration but with different affects on serum FSH levels. Inspired by the observation that adiposity accompanies the incremental increase in serum follicle stimulating hormone (FSH) levels in menopause, we hypothesized that gonadotrophin-releasing hormone (GnRH) antagonists which maximally inhibit FSH levels will associate with reduced adiposity and MS development compared to GNRH analogues and orchiectomy. Methods: In-vitro models of adipocyte differentiations were used to investigate FSH effects on lipid accumulation and expression of the rate limiting enzyme in this process-FAS. In-vivo models for adipogenesis and MS (LDL receptor KO mice) were used to investigate and compare the effects of orchiectomy (n=12), sham surgery (control, n=12), sham surgery plus GNRH antagonist (Degarelix, n=12) and sham surgery plus GNRH agonist (Enanton, n=12). Mice were also manipulated by two nutritional conditions (normal/high fat diet). Longitudinal weight gain (four month), visceral fat accumulation (CT measurements), fasting blood glucose, two hours glucose tolerance tests, serum triglycerides, FSH, LH, and testosterone levels were studied along with number and characteristics of aortic atherosclerotic plaques. Results: The lowest and highest serum FSH levels were recorded in mice treated with degarelix versus orchiectomy and significantly lower levels of FSH and LH in mice treated with degarelix versus enanthon were recorded. Mice treated with enantone gained significantly more weight and visceral fat compared to mice treated with degarelix. Significant lower levels of serum triglycerides and better response to glucose loading were recorded in mice treated with degarelix. Data on atherosclerotic plaques is currently processed and will be discussed, but preliminary analysis reveal lower plauque size in mice treated with degarelix. Conclusions: Usage of GNRH antagonists as ADT attenuates weight gain and development of the MS 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".