Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1994 Mar;93(3):1014–1019. doi: 10.1172/JCI117049

Calcium and protein kinetics in prepubertal boys. Positive effects of testosterone.

N Mauras 1, M W Haymond 1, D Darmaun 1, N E Vieira 1, S A Abrams 1, A L Yergey 1
PMCID: PMC294024  PMID: 8132741

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.

Full text

PDF
1019

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abrams S. A., Esteban N. V., Vieira N. E., Sidbury J. B., Specker B. L., Yergey A. L. Developmental changes in calcium kinetics in children assessed using stable isotopes. J Bone Miner Res. 1992 Mar;7(3):287–293. doi: 10.1002/jbmr.5650070307. [DOI] [PubMed] [Google Scholar]
  2. Abrams S. A., Esteban N. V., Vieira N. E., Yergey A. L. Dual tracer stable isotopic assessment of calcium absorption and endogenous fecal excretion in low birth weight infants. Pediatr Res. 1991 Jun;29(6):615–618. doi: 10.1203/00006450-199106010-00018. [DOI] [PubMed] [Google Scholar]
  3. Abrams S. A., Sidbury J. B., Muenzer J., Esteban N. V., Vieira N. E., Yergey A. L. Stable isotopic measurement of endogenous fecal calcium excretion in children. J Pediatr Gastroenterol Nutr. 1991 May;12(4):469–473. doi: 10.1097/00005176-199105000-00010. [DOI] [PubMed] [Google Scholar]
  4. Beaufrere B., Horber F. F., Schwenk W. F., Marsh H. M., Matthews D., Gerich J. E., Haymond M. W. Glucocorticosteroids increase leucine oxidation and impair leucine balance in humans. Am J Physiol. 1989 Nov;257(5 Pt 1):E712–E721. doi: 10.1152/ajpendo.1989.257.5.E712. [DOI] [PubMed] [Google Scholar]
  5. Copeland K. C., Kenney F. A., Nair K. S. Heated dorsal hand vein sampling for metabolic studies: a reappraisal. Am J Physiol. 1992 Nov;263(5 Pt 1):E1010–E1014. doi: 10.1152/ajpendo.1992.263.5.E1010. [DOI] [PubMed] [Google Scholar]
  6. Darmaun D., Déchelotte P. Role of leucine as a precursor of glutamine alpha-amino nitrogen in vivo in humans. Am J Physiol. 1991 Feb;260(2 Pt 1):E326–E329. doi: 10.1152/ajpendo.1991.260.2.E326. [DOI] [PubMed] [Google Scholar]
  7. Darmaun D., Manary M. J., Matthews D. E. A method for measuring both glutamine and glutamate levels and stable isotopic enrichments. Anal Biochem. 1985 May 15;147(1):92–102. doi: 10.1016/0003-2697(85)90013-2. [DOI] [PubMed] [Google Scholar]
  8. Darmaun D., Matthews D. E., Bier D. M. Physiological hypercortisolemia increases proteolysis, glutamine, and alanine production. Am J Physiol. 1988 Sep;255(3 Pt 1):E366–E373. doi: 10.1152/ajpendo.1988.255.3.E366. [DOI] [PubMed] [Google Scholar]
  9. Devogelaer J. P., De Cooman S., Nagant de Deuxchaisnes C. Low bone mass in hypogonadal males. Effect of testosterone substitution therapy, a densitometric study. Maturitas. 1992 Aug;15(1):17–23. doi: 10.1016/0378-5122(92)90057-b. [DOI] [PubMed] [Google Scholar]
  10. Ettinger B., Genant H. K., Cann C. E. Postmenopausal bone loss is prevented by treatment with low-dosage estrogen with calcium. Ann Intern Med. 1987 Jan;106(1):40–45. doi: 10.7326/0003-4819-106-1-40. [DOI] [PubMed] [Google Scholar]
  11. Evans W. J., Ivy J. L. Effects of testosterone propionate on hindlimb-immobilized rats. J Appl Physiol Respir Environ Exerc Physiol. 1982 Jun;52(6):1643–1647. doi: 10.1152/jappl.1982.52.6.1643. [DOI] [PubMed] [Google Scholar]
  12. Finkelstein J. S., Neer R. M., Biller B. M., Crawford J. D., Klibanski A. Osteopenia in men with a history of delayed puberty. N Engl J Med. 1992 Feb 27;326(9):600–604. doi: 10.1056/NEJM199202273260904. [DOI] [PubMed] [Google Scholar]
  13. Fisher E. C., Nelson M. E., Frontera W. R., Turksoy R. N., Evans W. J. Bone mineral content and levels of gonadotropins and estrogens in amenorrheic running women. J Clin Endocrinol Metab. 1986 Jun;62(6):1232–1236. doi: 10.1210/jcem-62-6-1232. [DOI] [PubMed] [Google Scholar]
  14. Forbes G. B. The effect of anabolic steroids on lean body mass: the dose response curve. Metabolism. 1985 Jun;34(6):571–573. doi: 10.1016/0026-0495(85)90196-9. [DOI] [PubMed] [Google Scholar]
  15. Griggs R. C., Halliday D., Kingston W., Moxley R. T., 3rd Effect of testosterone on muscle protein synthesis in myotonic dystrophy. Ann Neurol. 1986 Nov;20(5):590–596. doi: 10.1002/ana.410200506. [DOI] [PubMed] [Google Scholar]
  16. Horber F. F., Haymond M. W. Human growth hormone prevents the protein catabolic side effects of prednisone in humans. J Clin Invest. 1990 Jul;86(1):265–272. doi: 10.1172/JCI114694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jepson M. M., Bates P. C., Broadbent P., Pell J. M., Millward D. J. Relationship between glutamine concentration and protein synthesis in rat skeletal muscle. Am J Physiol. 1988 Aug;255(2 Pt 1):E166–E172. doi: 10.1152/ajpendo.1988.255.2.E166. [DOI] [PubMed] [Google Scholar]
  18. Johansen J. S., Riis B. J., Hassager C., Moen M., Jacobson J., Christiansen C. The effect of a gonadotropin-releasing hormone agonist analog (nafarelin) on bone metabolism. J Clin Endocrinol Metab. 1988 Oct;67(4):701–706. doi: 10.1210/jcem-67-4-701. [DOI] [PubMed] [Google Scholar]
  19. Johnston C. C., Jr, Miller J. Z., Slemenda C. W., Reister T. K., Hui S., Christian J. C., Peacock M. Calcium supplementation and increases in bone mineral density in children. N Engl J Med. 1992 Jul 9;327(2):82–87. doi: 10.1056/NEJM199207093270204. [DOI] [PubMed] [Google Scholar]
  20. Kiel D. P., Felson D. T., Anderson J. J., Wilson P. W., Moskowitz M. A. Hip fracture and the use of estrogens in postmenopausal women. The Framingham Study. N Engl J Med. 1987 Nov 5;317(19):1169–1174. doi: 10.1056/NEJM198711053171901. [DOI] [PubMed] [Google Scholar]
  21. Klibanski A., Biller B. M., Rosenthal D. I., Schoenfeld D. A., Saxe V. Effects of prolactin and estrogen deficiency in amenorrheic bone loss. J Clin Endocrinol Metab. 1988 Jul;67(1):124–130. doi: 10.1210/jcem-67-1-124. [DOI] [PubMed] [Google Scholar]
  22. Krotkiewski M., Kral J. G., Karlsson J. Effects of castration and testosterone substitution on body composition and muscle metabolism in rats. Acta Physiol Scand. 1980 Jul;109(3):233–237. doi: 10.1111/j.1748-1716.1980.tb06592.x. [DOI] [PubMed] [Google Scholar]
  23. MacLennan P. A., Brown R. A., Rennie M. J. A positive relationship between protein synthetic rate and intracellular glutamine concentration in perfused rat skeletal muscle. FEBS Lett. 1987 May 4;215(1):187–191. doi: 10.1016/0014-5793(87)80139-4. [DOI] [PubMed] [Google Scholar]
  24. Mauras N., Blizzard R. M., Link K., Johnson M. L., Rogol A. D., Veldhuis J. D. Augmentation of growth hormone secretion during puberty: evidence for a pulse amplitude-modulated phenomenon. J Clin Endocrinol Metab. 1987 Mar;64(3):596–601. doi: 10.1210/jcem-64-3-596. [DOI] [PubMed] [Google Scholar]
  25. Mauras N., Rogol A. D., Veldhuis J. D. Specific, time-dependent actions of low-dose ethinyl estradiol administration on the episodic release of growth hormone, follicle-stimulating hormone, and luteinizing hormone in prepubertal girls with Turner's syndrome. J Clin Endocrinol Metab. 1989 Nov;69(5):1053–1058. doi: 10.1210/jcem-69-5-1053. [DOI] [PubMed] [Google Scholar]
  26. Romshe C. A., Sotos J. F. The combined effect of growth hormone and oxandrolone in patients with growth hormone deficiency. J Pediatr. 1980 Jan;96(1):127–131. doi: 10.1016/s0022-3476(80)80348-9. [DOI] [PubMed] [Google Scholar]
  27. Rudman D., Goldsmith M., Kutner M., Blackston D. Effect of growth hormone and oxandrolone singly and together on growth rate in girls with X chromosome abnormalities. J Pediatr. 1980 Jan;96(1):132–135. doi: 10.1016/s0022-3476(80)80349-0. [DOI] [PubMed] [Google Scholar]
  28. Schoeller D. A., Klein P. D. A microprocessor controlled mass spectrometer for the fully automated purification and isotopic analysis of breath carbon dioxide. Biomed Mass Spectrom. 1979 Aug;6(8):350–355. doi: 10.1002/bms.1200060809. [DOI] [PubMed] [Google Scholar]
  29. Schwenk W. F., Berg P. J., Beaufrere B., Miles J. M., Haymond M. W. Use of t-butyldimethylsilylation in the gas chromatographic/mass spectrometric analysis of physiologic compounds found in plasma using electron-impact ionization. Anal Biochem. 1984 Aug 15;141(1):101–109. doi: 10.1016/0003-2697(84)90431-7. [DOI] [PubMed] [Google Scholar]
  30. Sokol R. Z., Palacios A., Campfield L. A., Saul C., Swerdloff R. S. Comparison of the kinetics of injectable testosterone in eugonadal and hypogonadal men. Fertil Steril. 1982 Mar;37(3):425–430. doi: 10.1016/s0015-0282(16)46108-x. [DOI] [PubMed] [Google Scholar]
  31. Stanhope R., Bommen M., Brook C. G. Constitutional delay of growth and puberty in boys: the effect of a short course of treatment with fluoxymesterone. Acta Paediatr Scand. 1985 May;74(3):390–393. doi: 10.1111/j.1651-2227.1985.tb10990.x. [DOI] [PubMed] [Google Scholar]
  32. Stanhope R., Buchanan C. R., Fenn G. C., Preece M. A. Double blind placebo controlled trial of low dose oxandrolone in the treatment of boys with constitutional delay of growth and puberty. Arch Dis Child. 1988 May;63(5):501–505. doi: 10.1136/adc.63.5.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Staten M. A., Bier D. M., Matthews D. E. Regulation of valine metabolism in man: a stable isotope study. Am J Clin Nutr. 1984 Dec;40(6):1224–1234. doi: 10.1093/ajcn/40.6.1224. [DOI] [PubMed] [Google Scholar]
  34. Stehle P., Zander J., Mertes N., Albers S., Puchstein C., Lawin P., Fürst P. Effect of parenteral glutamine peptide supplements on muscle glutamine loss and nitrogen balance after major surgery. Lancet. 1989 Feb 4;1(8632):231–233. doi: 10.1016/s0140-6736(89)91254-3. [DOI] [PubMed] [Google Scholar]
  35. Vinnars E., Bergstöm J., Fürst P. Influence of the postoperative state on the intracellular free amino acids in human muscle tissue. Ann Surg. 1975 Dec;182(6):665–671. doi: 10.1097/00000658-197512000-00001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wernerman J., Hammarqvist F., Vinnars E. Alpha-ketoglutarate and postoperative muscle catabolism. Lancet. 1990 Mar 24;335(8691):701–703. doi: 10.1016/0140-6736(90)90811-i. [DOI] [PubMed] [Google Scholar]
  37. Yergey A. L., Abrams S. A., Vieira N. E., Eastell R., Hillman L. S., Covell D. G. Recent studies of human calcium metabolism using stable isotopic tracers. Can J Physiol Pharmacol. 1990 Jul;68(7):973–976. doi: 10.1139/y90-147. [DOI] [PubMed] [Google Scholar]
  38. Yergey A. L., Vieira N. E., Covell D. G. Direct measurement of dietary fractional absorption using calcium isotopic tracers. Biomed Environ Mass Spectrom. 1987 Nov;14(11):603–607. doi: 10.1002/bms.1200141105. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES