Moshe Phillip1, 3 , Gila Maor2, Sara Assa1, Aviva Silbergeld1 and Yael Segev3
(1) The Felsenstein Medical Research Center, Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children’s Medical Center, Petach Tikva, Israel
(2) Department of Morphology Science, The Rappaport Faculty of Medicine, Technion, Haifa, Israel
(3) Molecular Endocrine Laboratory, Ben-Gurion University of the Negev, Beer-Sheva, Israel
Received: 27 February 2001 Revised: 2 June 2001 Accepted: 9 July 2001
Abstract 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
Moshe Phillip (Director)
Email:
Mosheph@post.tau.ac.il
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If I am reading that right-the group that recieved the high dose of test-the test had an inhibitory effect on gh.