ANDROGENIC REGULATION OF SEX DIFFERENCES IN ADAPTATIONS TO AGING AND EXERCISE IN RATS
Bibliographic record
Abstract
Sex differences in vertebrate muscle morphology are largely mediated by gonadal androgens and the canonical androgen receptor (AR), as loss of function AR mutations result in feminized phenotype in male rats. However, genetic AR ablation mouse models using sedentary males at single timepoint collections provide conflicting evidence to the necessity of skeletal muscle AR in maintaining body composition and muscle phenotype. Considering these fundamental gaps in knowledge, experiments were performed using a transgenic rat model of muscle-specific AR overexpression (HSAAR), under a human skeletal alpha-actin promoter, to understand the impact of supraphysiological AR content on male and female body composition and skeletal limb muscle phenotype in response to chronic endurance training as well as growth- and age-related changes across the lifespan, under an endogenous sex steroid environment. Chapter 2 explored the impacts of HSAAR on body composition and muscle phenotype in emerging adult male and female rats undergoing 9-weeks of chronic endurance training. Sex showed dependent effects on exercise-induced changes to lean, bone, and total mass, while HSAAR increased lean mass and glycolytic myofiber size in both sexes. However, we did not observe combined effects of endurance training and muscle-specific AR overexpression on any measured outcomes. Chapter 3 coordinated a lifespan timeline for the appearance and fluctuation of testosterone and AR on myogenic lineage, myofiber organization, and satellite cell activation. This work underscored a benefit in interdisciplinary research between neuroendocrinology and muscle physiology. Chapter 4 identified the ontogeny of skeletal muscle AR protein in oxidative and glycolytic muscle, and examined the effects of HSAAR in mediating body composition, muscle mass, and adiposity across aging male and female rats. Our findings support other work that emergence of major sex difference within muscle, adipose, and whole-body composition appear at puberty, yet we add that these major sexual development changes do not seem to occur in tandem with changes in expression of muscle-specific AR. Additionally, we show that HSAAR increases glycolytic, but not oxidative, skeletal muscle mass in males only across adulthood, while attenuating aging-related adipose accretion in both sexes during adulthood. Taken together, this thesis highlights that sex differences in muscle and body composition during periods of sexual development or post-endurance training, do not seem to be mediated by significant changes to skeletal muscle AR protein expression. We also highlight that significantly lower circulating androgens in adult females do not preclude females from obtaining the HSAAR-mediated increase in lean mass and reduction in adiposity, highlighting the strong responsiveness of both sexes to elevated skeletal muscle AR in an age-dependent manner.
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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 | 0.001 | 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) | 0.002 | 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".