This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Maor, G. Articles by Phillip, M. Search for Related Content PubMed PubMed Citation Articles by Maor, G. Articles by Phillip, M.

Testosterone Stimulates Insulin-Like Growth Factor-I and Insulin-Like Growth Factor-I-Receptor Gene Expression in the Mandibular Condyle—A Model of Endochondral Ossification

Department of Morphological Sciences (G.M.), The B. Rappapport Faculty of Medicine, Technion, Haifa 31096, Israel; Molecular Endocrine Laboratory Soroka Medical Center (Y.S., M.P.), Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel; and Felsenstein Medical Research Center (M.P.), Institute for Endocrinology and Diabetes, Schneider Children’s Medical Center, Beilinson Campus, Petach Tikva 49202, Israel

Address all correspondence and requests for reprints to: Prof. Moshe Phillip, Director, Institute for Endocrinology and Diabetes, Schneider Children’s Medical Center of Israel, 14 Kaplan Street, Petach-Tikva, 49202, Israel.

Puberty is associated with an increase in the plasma concentration of sex steroids, GH, and insulin-like growth factor-I (IGF-I). Gonadal steroid hormones are important for the normal pubertal growth spurt and skeletal growth. The mechanism by which gonadal steroids induce skeletal growth is still not fully understood. To better understand the direct effect sex steroids have on bone growth, we studied an isolated organ culture system of the mandibular condyle, derived from 3.5–5.5-week-old male and female mice. We found that testosterone 10^-6 M, but not estradiol, stimulated thymidine incorporation into the DNA of male-derived condyle. Three days of testosterone treatment doubled the condyle size and increased the chondroprogenitor zone, while maintaining the normal gradient of the developing chondrocytes. Immunohistochemistry and in situ hybridization techniques showed that testosterone stimulated IGF-I and IGF-I-R and their messenger RNAs (mRNAs) mainly in the mature chondrocyte layer. Immunoneutralization of IGF-I in the testosterone-treated condyle caused the disappearance of the chondroblast and young chondrocyte layers, though the progenitor cell layer remained almost unaffected. Overtreatment with testosterone (dose or duration) accelerated condylar ossification. In the presence of testosterone 10^-5 M (high dose), calcification "climbs" up to the chondroprogenitor zone, and most of the condylar chondrocytes are replaced by bone tissue. Similar changes occurred after 7 days of testosterone treatment (long duration) with 10^-6 M. In conclusion, testosterone stimulates growth and local production of IGF-I and IGF-I-R in chondrocyte cell layers of an isolated organ culture of mice mandibular condyle. Part of the effect testosterone has on condylar growth is mediated by IGF-I.

This article has been cited by other articles:

				I. Mohamed and J. K Yeh Alfacalcidol prevents aromatase inhibitor (Letrozole)-induced bone mineral loss in young growing female rats J. Endocrinol., August 1, 2009; 202(2): 317 - 325. [Abstract] [Full Text] [PDF]

				G. Liu, H. Kawaguchi, T. Ogasawara, Y. Asawa, J. Kishimoto, T. Takahashi, U.-i. Chung, H. Yamaoka, H. Asato, K. Nakamura, et al. Optimal Combination of Soluble Factors for Tissue Engineering of Permanent Cartilage from Cultured Human Chondrocytes J. Biol. Chem., July 13, 2007; 282(28): 20407 - 20415. [Abstract] [Full Text] [PDF]

				T. Munzer, C. J. Rosen, S.M. Harman, K. M. Pabst, C. St. Clair, J. D. Sorkin, and M. R. Blackman Effects of GH and/or sex steroids on circulating IGF-I and IGFBPs in healthy, aged women and men Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E1006 - E1013. [Abstract] [Full Text] [PDF]

				A S Chagin, D Chrysis, M Takigawa, E M Ritzen, and L Savendahl Locally produced estrogen promotes fetal rat metatarsal bone growth; an effect mediated through increased chondrocyte proliferation and decreased apoptosis J. Endocrinol., February 1, 2006; 188(2): 193 - 203. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, J. N. Roemmich, E. J. Richmond, A. D. Rogol, J. C. Lovejoy, M. Sheffield-Moore, N. Mauras, and C. Y. Bowers Endocrine Control of Body Composition in Infancy, Childhood, and Puberty Endocr. Rev., February 1, 2005; 26(1): 114 - 146. [Abstract] [Full Text] [PDF]

				H. Yoshizato, M. Tanaka, N. Nakai, N. Nakao, and K. Nakashima Growth Hormone (GH)-Stimulated Insulin-Like Growth Factor I Gene Expression Is Mediated by a Tyrosine Phosphorylation Pathway Depending on C-Terminal Region of Human GH Receptor in Human GH Receptor-Expressing Ba/F3 Cells Endocrinology, January 1, 2004; 145(1): 214 - 220. [Abstract] [Full Text] [PDF]

				B. C. J. van der Eerden, M. Karperien, and J. M. Wit Systemic and Local Regulation of the Growth Plate Endocr. Rev., December 1, 2003; 24(6): 782 - 801. [Abstract] [Full Text] [PDF]

				H. Yu, X.-O. Shu, B. D. L. Li, Q. Dai, Y.-T. Gao, F. Jin, and W. Zheng Joint Effect of Insulin-like Growth Factors and Sex Steroids on Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., October 1, 2003; 12(10): 1067 - 1073. [Abstract] [Full Text] [PDF]

				C. H. Gravholt, J. Frystyk, A. Flyvbjerg, H. Orskov, and J. S. Christiansen Reduced free IGF-I and increased IGFBP-3 proteolysis in Turner syndrome: modulation by female sex steroids Am J Physiol Endocrinol Metab, February 1, 2001; 280(2): E308 - E314. [Abstract] [Full Text] [PDF]

				J. Van Wyk Insulin-Like Growth Factors and Skeletal Growth: Possibilities for Therapeutic Interventions J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4349 - 4354. [Full Text]

				Estrogen: Consequences and Implications of Human Mutations in Synthesis and Action J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4677 - 4694. [Abstract] [Full Text]

				F. Gori, L. C. Hofbauer, C. A. Conover, and S. Khosla Effects of Androgens on the Insulin-Like Growth Factor System in an Androgen-Responsive Human Osteoblastic Cell Line Endocrinology, December 1, 1999; 140(12): 5579 - 5586. [Abstract] [Full Text]

				M. I. Lewis, G. D. Horvitz, D. R. Clemmons, and M. Fournier Role of IGF-I and IGF-binding proteins within diaphragm muscle in modulating the effects of nandrolone Am J Physiol Endocrinol Metab, February 1, 2002; 282(2): E483 - E490. [Abstract] [Full Text] [PDF]