Testosterone stimulates growth of tibial epiphyseal growth plate and insulin-like growth factor-1 receptor abundance in hypophysectomized and castrated rats.
Puberty is associated with an increase 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 microg/(kg x d) of hydrocortisone and 15 microg/(kg x d) of levothyroxine sodium. Groups A and B were also treated with daily sc injections of 10 microg of testosterone/100 g of body wt and 100 microg 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 EGP width of 472.3+/-39 microm in the intact animals but only 336.9+/-1.6 microm 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.
Phillip
M
M
The Felsenstein Medical Research Center, Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center, Petach Tikva, Israel. Mosheph@post.tau.ac.il
Maor
G
G
Assa
S
S
Silbergeld
A
A
Segev
Y
Y
D000818:Animals; D004838:Epiphyses / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D013006:Growth Hormone / Q000097:blood; D006132:Growth Plate / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D009919:Orchiectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology*; D013977:Tibia / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism
D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1