Androgen receptor modulation does not affect longitudinal growth of cultured fetal rat metatarsal bones.
BACKGROUND
Systemic administration of the nonaromatizable androgen oxandrolone stimulates growth in girls with Turner syndrome and boys with a constitutional delay of growth and puberty. It is unknown if oxandrolone acts locally at the growth plate level to stimulate longitudinal bone growth.


METHODS
Metatarsal bones from female and male rat fetuses (day E20) were cultured for 14 days in the presence of oxandrolone, testosterone or the androgen receptor (AR) antagonist flutamide with/without insulin-like growth-factor-I (IGF-I) or charcoal-treated serum.


RESULTS
The AR was found to be expressed in both male and female fetal rat metatarsal bones. Neither oxandrolone nor testosterone had any effect on metatarsal bone growth when tested at a wide concentration range (1 nM to 10 microM), not even in the presence of IGF-I (100 ng/ml) or charcoal-treated serum (10%). Bone growth was also unaffected when the AR was blocked by flutamide. Control experiments confirmed that metatarsal bone growth was significantly stimulated by IGF-I (p < 0.001).


CONCLUSIONS
Modulation of AR activity in the fetal rat growth plate does not affect linear bone growth. Extrapolating from these in vitro data, it could be speculated that oxandrolone stimulates longitudinal bone growth in treated children by acting indirectly rather than directly through AR activation in growth plate chondrocytes.
Chagin
Andrei S
AS
Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden. achagin@partners.org
Vannesjö
Johanna
J
Sävendahl
Lars
L
D000818:Animals; D001846:Bone Development / Q000187:drug effects; D005260:Female; D005333:Fetus; D005485:Flutamide / Q000494:pharmacology; D008297:Male; D008682:Metatarsal Bones / Q000196:embryology / Q000254:growth & development*; D009924:Organ Culture Techniques; D010074:Oxandrolone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000187:drug effects / Q000502:physiology*; D013739:Testosterone / Q000494:pharmacology
D011944:Receptors, Androgen; D013739:Testosterone; D005485:Flutamide; D010074:Oxandrolone