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Calcium and protein kinetics in prepubertal boys. Positive effects of testosterone
N Mauras1, M W Haymond, D Darmaun
1Nemours Children's Clinic, Jacksonville, Florida 32207.
Insights
Short-term testosterone therapy in prepubertal boys significantly boosts calcium retention and bone anabolism. It also enhances protein synthesis and growth hormone levels, indicating anabolic effects.
Area of Science:
- Endocrinology
- Pediatric Endocrinology
- Metabolic Research
Background:
- Prepubertal short stature is a clinical concern.
- Testosterone's anabolic effects are well-documented in adults.
- Limited data exists on testosterone's impact on calcium and protein metabolism in prepubertal children.
Purpose of the Study:
- To investigate the effects of short-term testosterone administration on calcium and protein metabolism in healthy prepubertal short boys.
- To assess changes in calcium absorption, retention, and bone flux.
- To evaluate the impact on protein synthesis and breakdown markers.
Main Methods:
- Six healthy prepubertal short boys (mean age 12.9 yr) received testosterone enanthate (approx. 3 mg/kg) for 4-6 weeks.
- Stable isotopes (L-[1-13C]leucine, L-[2-15N]glutamine) and calcium isotopes (42Ca, 44Ca) were used for metabolic tracing.
- Measurements included serum hormone levels, calcium absorption and retention, and amino acid kinetics.
Main Results:
- Testosterone administration increased serum testosterone, peak, and total growth hormone concentrations.
- Net calcium absorption and retention significantly increased (P < .05).
- Protein anabolism markers improved, with increased nonoxidative leucine disposal (protein synthesis) and decreased leucine oxidation.
- Glutamine appearance rate increased, driven by enhanced de novo synthesis.
Conclusions:
- Short-term testosterone therapy significantly enhances calcium retention and bone anabolism in prepubertal boys.
- Testosterone administration positively impacts whole-body protein and calcium anabolism.
- Observed effects may be due to direct androgen action, potentiation of growth hormone, or a combination of factors.
Abstract:
We investigated the effects of 4-6-wk administration of testosterone on calcium and protein metabolism in six healthy prepubertal short boys (mean age +/- SE = 12.9 +/- 0.6 yr). At baseline, subjects received a 4-h infusion of L-[1-13C]leucine and L-[2-15N]glutamine, and were given 42Ca intravenously, and 44Ca PO. Testosterone enanthate (approximately 3 mg/kg) was given I.M. 2 wk apart (two doses n = 5, three doses n = 1), and the study was repeated 4-5 d after the last injection. After testosterone therapy, there were significant increases in serum testosterone and mean peak and total growth hormone concentrations. Net calcium absorption (Va) and retention (Vbal) also increased (Va 13.3 +/- 2.3 vs 21.5 +/- 2.3; mg.kg-1.d-1, Vbal 8.0 +/- 2.1 vs 16.6 +/- 2.5, mg.kg-1.d-1, P < .05 both), as well as Ca's net forward flow into bone and total exchangeable pool (16 and 20%, respectively). The rate of appearance of leucine (an indicator of proteolysis) increased by 17.6 +/- 5.9%, P = 0.036. Leucine oxidation decreased by 48.6 +/- 8.0%, P = 0.004; thus, nonoxidative leucine disappearance, which estimates protein synthesis, increased significantly by 34.4 +/- 7.7%, P = 0.009. Glutamine's rate of appearance also increased (+32%), mostly through enhanced glutamine de novo synthesis (+42%). In conclusion, short term testosterone administration significantly increases calcium's retention and net forward flow into bone in prepubertal humans, as well as whole body estimates of protein and calcium anabolism. These effects may represent a pure androgen effect, an amplification of growth hormone's action or some combination of these factors.
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