Aging attenuates both the regularity and joint synchrony of LH and testosterone secretion in normal men: analyses via a model of graded GnRH receptor blockade
Bibliographic record
Abstract
Testosterone (T) secretion declines in the aging male, albeit for unknown reasons. From an ensemble perspective, repeated incremental signaling among gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and T is required to maintain physiological androgen availability. Pattern-regularity statistics, such as univariate approximate entropy (ApEn) and bivariate cross-ApEn, provide specific and sensitive model-free measurement of altered multi-pathway control. The present study exploits partial muting of one pathway (GnRH drive) to appraise adaptive regulation of LH and T secretion in young and aging individuals. Analyses comprised 100 paired 18-h LH and T concentration time series obtained in 25 healthy men ages 20-72 yr each administered placebo and three graded doses of a specific GnRH-receptor antagonist. Graded blockade of GnRH drive increased the individual regularity of LH and T secretion and the synchrony of LH-T feedforward and T-LH feedback in the cohort as a whole (P<0.001 for each). However, age markedly attenuated ganirelix-induced enhancement of univariate T orderliness and bivariate LH-T feedback and T-LH feedback synchrony (P <or= 0.0025). In summary, the present analyses support the thesis that aging disrupts coordinate control of T secretion, LH-T feedforward, and T-LH feedback in healthy men. Thus the experimental strategy of stepwise silencing of an agonistic pathway may have utility in dissecting the bases of altered neurohormonal linkages in other systems.
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How this classification was reachedexpand
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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.002 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".