Testosterone effect on growth and growth mediators of the CH-IGF-I axis inthe liver and epiphyseal growth plate of juvenile rats

Several studies have suggested that testosterone may have a direct, GH-inde pendent effect on growth. In order to assess possible mechanism(s) whereby testosterone exerts its growth-promoting effect, we evaluated its effect on growth mediators of the GH-IGF-I axis, in both the liver and the epiphysea l growth plate (EGP). Testosterone was administered to peripubertal rats an d the responses of mRNA of GH receptor, IGF-I, IGF-I receptor and IGF-bindi ng proteins-1 and -3 (IGFBP-1 and IGFBP-3) as well as circulating IGF-I wer e evaluated in two time-related models: over 12 h after a single injection (short-term study) and 10 days after continuous administration (long-term s tudy). Rats in the short-term study were castrated and were killed 1, 4, 6 and 12 h post injection. Rats in the long-term study were divided into two groups: castrated vs castrated and hypophysectomized, in order to assess th e effect of testosterone in the presence and absence of GH. mRNA levels wer e determined by RNase protection assay, and serum IGF-I by RIA. Testosterone enhanced weight gain in the rats treated for 10 days, a change that was similar in the presence or absence of GH. This effect was relativ ely small, however, by comparison with the total weight gained without test osterone. Testosterone had no effect on hepatic IGF-I mRNA abundance but in duced a reduction in circulating IGF-I levels, in both the short- and long- term study. Testosterone had no effect on hepatic GH receptor and IGFBP-3 m RNA levels but resulted in a transient, short-term elevation in IGFBP-1 mRN A levels that was maximal 4 h post injection. In the EGP, neither testosterone administration nor hypophysectomy had any effect on IGF-I and IGF-I receptor mRNA levels. However, testosterone incre ased CH receptor mRNA abundance after 10 days of continuous administration in hypophysectomized rats only. These data suggest that the effect of testosterone on growth (as assessed b y weight gain) is small and is not mediated by changes in hepatic gene expr ession of IGF-I, IGF-I receptor, IGFBP-1, IGFBP-3 or circulating IGF-I. At the EGP, the testosterone effect on linear growth is not mediated through c hanges in mRNA abundance of IGF-I and IGF-I receptor. The small but signifi cant elevation of GH receptor mRNA levels in hypophysectomized rats may sug gest a testosterone-mediated augmentation of a GH effect at the target orga n.