The aromatase inhibitor letrozole increases epiphyseal growth plate height and tibial length in peripubertal male mice

The aromatase inhibitor letrozole increases epiphyseal growth plate height and tibial length in peripubertal male mice

Sex hormones may influence longitudinal growth, either indirectly, by affecting the growth-hormone-insulin-like growth factor I (IGF-I) axis, or directly, by affecting changes within the epiphyseal growth plate (EGP). The aim of the present study was to investigate the effects of letrozole, an aroma...

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Bibliographic Details
Published in:Journal of endocrinology Vol. 182; no. 1; pp. 165 - 172
Main Authors: Eshet, R, Maor, G, Ben Ari, T, Ben Eliezer, M, Gat-Yablonski, G, Phillip, M
Format: Journal Article
Language:English
Published: Colchester BioScientifica 01-07-2004
Portland Press
Subjects:
Animals
Aromatase - analysis
Aromatase Inhibitors
Biological and medical sciences
Body Weight - drug effects
Collagen - analysis
Collagen Type II - analysis
Collagen Type X - analysis
Fundamental and applied biological sciences. Psychology
Growth Plate - drug effects
Immunohistochemistry - methods
Letrozole
Male
Mice
Mice, Inbred ICR
Nitriles - pharmacology
Receptor, IGF Type 1 - analysis
Sexual Maturation
Skeleton and joints
Tail - drug effects
Tibia - chemistry
Tibia - drug effects
Tibia - growth & development
Triazoles - pharmacology
Vertebrates: osteoarticular system, musculoskeletal system
Cell proliferation
Enzyme
Cytochrome P450
Rodentia
Enzyme inhibitor
Male
Estrogen synthase
Cell differentiation
Osteoarticular system
Vertebrata
Mammalia
Epiphyseal cartilage
Mouse
Prepuberty
Tibia
Morphological analysis
Bone
Non steroid compound
Letrozole
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Summary:Sex hormones may influence longitudinal growth, either indirectly, by affecting the growth-hormone-insulin-like growth factor I (IGF-I) axis, or directly, by affecting changes within the epiphyseal growth plate (EGP). The aim of the present study was to investigate the effects of letrozole, an aromatase inhibitor, on longitudinal growth and changes in the EGP in vivo. Eighteen peripubertal male mice were divided into three groups. The first group was killed at baseline, the second was injected with letrozole (Femara) s.c., 2 mg/kg body weight/day, for 10 days, and the third was injected with the vehicle alone. Serum testosterone levels were found to be significantly higher in the treated group than in the controls. Letrozole induced a significant increase in body weight, tail length and serum growth hormone level, but had no significant effect on the level of serum IGF-I. On histomorphometric study, there was a significant increase (12%) in EGP height in the treated animals compared with controls. Immunohistochemistry showed a 3.4-fold letrozole-induced increase in the proliferation of the EGP chondrocytes, as estimated by the number of proliferation cell nuclear antigen-stained cells, and a decrease in the differentiation of the EGP chondrocytes, as estimated by type X collagen staining. Letrozole did not interfere with type II collagen levels. The study group also showed a twofold increase in the number of IGF-I receptor-positive cells compared with controls. In conclusion, the aromatase inhibitor, letrozole, appears to increase the linear growth potential of the EGP in mice.
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content type line 23
ISSN:0022-0795
1479-6805
DOI:10.1677/joe.0.1820165