, Volume 16, Issue 1, pp 1–6 | Cite as

Testosterone stimulates growth of tibial epiphyseal growth plate and insulin-like growth factor-1 receptor abundance in hypophysectomized and castrated rats

  • Moshe Phillip
  • Gila Maor
  • Sara Assa
  • Aviva Silbergeld
  • Yael Segev


Puberty is associated with an increased in the plasma concentration of sex steroids, growth hormone (GH), and insulin-like growth factor-1 (IGF-1). Gonadal steroid hormones are important for the normal pubertal growth spurt and skeletal growth. The mechanism by which gonadal steroids induces skeletal growth is still not fully understood. To study the GH-independent effect of testosterone on growth, we investigated the effect of testosterone injections on the tibial epiphyseal growth plate (EGP) in an in vivo model of hypophysectomized and castrated male rats. Four groups (six animals each) of 28-d-old male rats were studied. Groups A, B, and C were hypophysectomized and castrated and received 500 µg/(kg·d) of hydrocortisone and 15 µg/(kg·d) of levothyroxine sodium. Groups A and B were also treated with daily sc injections of 10 µg of testosterone/100 g of body wt, and 100 µg of testosterone/100 g of body wt, respectively, for 7 d. Group C was injected with vehicle alone. Group D were intact animals injected with saline (controls). Animals were sacrificed on 8 d. As expected, serum GH levels were found to be very low (1.13±0.1 ng/mL) in the hypophysectomized animals (group C, hypopit), and testosterone treatment did not change them significantly. Serum IGF-1 decreased from 502.9± 13 ng/mL in group D to 167±41.4 ng/mL in group C (p<0.001). Testosterone therapy had no stimulatory effect on serum IGF-1 levels in the hypopit + low-dose group (A) (220±94.8 ng/mL) and had an inhibitory effect in the hypopit + high-dose group (B) (39.3±17.5). Histomorphometric determinations demonstrated an EGF width of 472.3±39 µm in the intact animals but only 336.9±1.6 µm in the hypopit group (C) (p<0.01). High-dose testosterone treatment (group B) significantly increased the EGP width (to 438.8±27.8), (p<0.001), whereas low-dose testosterone (group A) did not. Immunohistochemistry studies revealed that the levels of IGF-1 in the EGP of the control animals were almost negligible and that testosterone did not change them. However, testosterone increased in a dose-dependent manner the abundance of IGF-1 receptor EGP. We conclude that testosterone has a direct, local, GH-independent effect on the EGP growth and IGF-1 receptor abundance.

Key Words

Testosterone IGF-1 epiphyseal growth plate 


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  1. 1.
    Bala, R. M., Lopatka, J., Leung, A., McCoy, E., and McArthur, R. G. (1981). J. Clin. Endocrinol. Metab. 52, 508–511.PubMedGoogle Scholar
  2. 2.
    Luna, A. M., Wilson, D. M., Wibbelsman, C. J., Brown, R. C., Nagashima, R. J., Hintz, R. L., and Rosenfeld, R. G. (1983). J. Clin. Endocrinol. Metab. 57, 268–271.PubMedGoogle Scholar
  3. 3.
    Thompson, R. G., Rodriguez, A., Kowarski, A., Migeon, C. J., and Blizzard, R. M. (1972). J. Clin. Endocrinol. Metab. 35, 334–337.Google Scholar
  4. 4.
    Brook, C. G. (1988). Clin. Endocrinol. (Oxf.). 39, 197–204.Google Scholar
  5. 5.
    Mauras, N., Rogol, A. D., Haymond, M. W., and Veldhuis, J. D. (1996). Horm. Res. 45, 74–80.PubMedCrossRefGoogle Scholar
  6. 6.
    Nieves-Rivera, F., Rogol, A. D., Veldhuis, J. D., Branscom, D. K., Martha, P. M. Jr., and Clarke, W. L. (1993). J. Clin. Endocrinol. Metab. 77, 638–643.PubMedCrossRefGoogle Scholar
  7. 7.
    Caufriez, A. (1997). Eur. J. Obstet. Gynecol. Reprod. Biol. 71, 215–217.PubMedCrossRefGoogle Scholar
  8. 8.
    Craft, W. H. and Underwood, L. E. (1984). Clin. Endocrinol. (Oxf.) 20, 549–554.Google Scholar
  9. 9.
    Keenam, B. S., Richards, G. E., Ponder, S. W., Dalas, J. S., Nagamani, M., and Smith, E. R. (1993). J. Clin. Endocrinol. Metab. 76, 996–1001.CrossRefGoogle Scholar
  10. 10.
    Attie, K. M., Ramirez, N. R., Conte, F. A., Kaplan, S. L., and Grumbach, M. M. (1990). J. Clin. Endocrinol. Metab. 71, 975–983.PubMedCrossRefGoogle Scholar
  11. 11.
    Maor, G., Segev, Y., and Phillip, M. (1999). Endocrinology 140, 1901–1910.PubMedCrossRefGoogle Scholar
  12. 12.
    Laron, Z., Sarel, R., and Pertzelan, A. (1980). Eur. J. Pediatr. 134, 79–83.PubMedCrossRefGoogle Scholar
  13. 13.
    Rivarola, M. A., Phillips, J. A. III, Migeon, C. J., Heinrich, J. J., and Hjelle, B. J. (1984). J. Clin. Endocrinol. Metab. 59, 34–40.PubMedGoogle Scholar
  14. 14.
    Young, I. R., Mesiano, S., Hintz, R., Caddy, D. J., Ralph, M. M., Brown, C. A., and Thorburn, G. D. (1989). J. Endocrinol. 121, 563–570.PubMedGoogle Scholar
  15. 15.
    Klindt, J., Ford, J. J., and Macdonald, G. J. (1990). J. Endocrinol. 127, 249–256.PubMedGoogle Scholar
  16. 16.
    Phillip, M., Palese, T., Hernandez, E. R., Roberts, C. T., LeRoith, J. D., and Kowarski, A. A. (1992). Endocrinology 130, 2865–2870.PubMedCrossRefGoogle Scholar
  17. 17.
    Zung, A., Phillip, M., Chalew, S. A., Palese, T., Kowarski, A. A., and Zadik, Z. (1999). J. Mol. Endocrinol. 23, 209–221.PubMedCrossRefGoogle Scholar
  18. 18.
    Eriksen, E. F., Colvard, D. S., Berg, N. J., Graham, M. L., Mann, K. G., Spels, B., Berg, T. C., and Riggs, B. L. (1988). Science 241, 84–86.PubMedCrossRefGoogle Scholar
  19. 19.
    Tkigawa, M., Okawa, T., Pan, H., Aoki, Takahashi, K., Zue, J., Suzuki, F., and Kinoshita, A. (1997). Endocrinology 138, 4390–4400.CrossRefGoogle Scholar
  20. 20.
    Hernandez Sanchez, C., Werner, H., Roberts, C. T. Jr., Woo, E. J., Rosenthal, S. M., and LeRoith, D. (1997). J. Biol. Chem. 272, 4663–4670.PubMedCrossRefGoogle Scholar
  21. 21.
    Klaus, G., Weber, L., Rodriguez, J., Fernandez, P., Klein, T., Grruloch-Henn, J., Hugel, U., Ritz, E., and Mehls, P. (1998). Kidney Int. 53, 1152–1161.PubMedCrossRefGoogle Scholar
  22. 22.
    Daws, M. R., Westley, B. R., and May, F. E. (1996). Endocrinology 137, 1177–1186.PubMedCrossRefGoogle Scholar
  23. 23.
    Le Roith, D., Werner, H., Neuenschwander, S., Kalebic, T., and Helman, L. J. (1995). Ann. NY Acad. Sci. 766, 402–406.CrossRefGoogle Scholar
  24. 24.
    Bondy, C., Werner, H., Roberts, C. J., and Le Roith, D. (1992). Neuroscience 46, 619–626.CrossRefGoogle Scholar
  25. 25.
    Moreno, B., Rodriguez, N. J., Perez, C. A., and Santos, A. (1997). Endocrinology 137, 1194–1203.CrossRefGoogle Scholar
  26. 26.
    Eshet, R., Klinger, B., Silbergeld, A., and Laron, Z. (1993). Breast Cancer Res. Treat. 47, 235–253.Google Scholar
  27. 27.
    Sepp-Lorenzo, L. (1998). Breast Cancer Res. Treat. 47, 235–253.CrossRefGoogle Scholar
  28. 28.
    Blum, W. T. and Breier, B. H. (1994). Growth Regul. 4 (Suppl 1), 11–19.PubMedGoogle Scholar
  29. 29.
    Sinha, Y. N., Selby, F. W., Lewis, U. J., and Vanderlaan, W. P. (1972). Endocrinology 91, 784–792.PubMedGoogle Scholar

Copyright information

© Humana Press Inc 2001

Authors and Affiliations

  • Moshe Phillip
    • 1
    • 3
  • Gila Maor
    • 2
  • Sara Assa
    • 1
  • Aviva Silbergeld
    • 1
  • Yael Segev
    • 3
  1. 1.The Felsenstein Medical Research Center, Institute for Endocrinology and DiabetesNational Center for Childhood Diabetes, Schneider Children’s Medical CenterPetach TikvaIsrael
  2. 2.Department of Morphology ScienceThe Rappaport Faculty of Medicine, TechnionHaifaIsrael
  3. 3.Molecular Endocrine LaboratoryBen-Gurion University of the NegevBeer-ShevaIsrael

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