|Budget Amount *help
¥1,800,000 (Direct Cost : ¥1,800,000)
Fiscal Year 1997 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1996 : ¥1,000,000 (Direct Cost : ¥1,000,000)
*EFFECTS OF LONG-TERM GONADOTROPIN-RELEASING HORMONE ANALOGUE TREATMENT ON SOMATIC GROWTE AND CIRCULATING INSULIN-LIKE GROWTH FACTOR-1 LEVELS IN THE GROWTH HOIRMONE DEFICIENT RAT*
[AIM] Previous studies suggest that gonadectomy lead to slight reduction of body weight gain with increased or unchanged insulin-like growth factor (IGF) -1 levels in male rats, and increased both weight gain and IGF-1 levels in female rats. We speculate that perinatal gonadal steroids and elevated gonadatropins may affect growth and the growth hormone (GH) /IGF-1 axis. This study was designed to evaluate the effects of hypogonadotropic gonadal suppression since neonatal period on somatic growth and serum IGF-1 levels in rats.
[MATERIALS and METHODS] Spontaneous dwarf rat was used as a model of complete GH deficiency (GHD), and Sprague-Dawlry (SD) rat was used as control.Gonadotropin-releasing hormone analogue (GnRHa : Leuprolide acetate depot, 2mg/kg) was administered subcutaneously every 3 weeks. Treatment wa
s started within 48 hours after birth and terminated at 15 weeks of age. Body weight, serum testosterone (T)or estradiol (E2), and IGF-1 were evaluated, and effects were compared with saline treated rats.
[RESULTS] Serum T or E2 were significantly reduced by the GnRHa treatment. Body weight at 15 was not different between the groups in both lines of male rats (saline vs GnRHa ; 551(]SY.+-。[)43 vs 561(]SY.+-。[)27g in SD rats, 88(]SY.+-。[))15 vs 91(]SY.+-。[)12g in GHD rats). While in famale, markedly greater body weight in the GnRHa group was observed in SD rats (285(]SY.+-。[)7 vs 351(]SY.+-。[))31g, p<0.01), but not in GHD rats (79(]SY.+-。[)15 vs 79ア16g). Serum IGF-1 was not different between the groups in both rats of both male (957 ア173 vs 976(]SY.+-。[)97ng/ml in SD rats, 10.3(]SY.+-。[)1.0 vs 11.5(]SY.+-。[)1.3ng/ml in GHD rats) and female (460(]SY.+-。[)167 vs 534(]SY.+-。[)74ng/ml in SD rats, 11.6(]SY.+-。[)3.1 vs 11.0(]SY.+-。[))1.8ng/ml in GHD rats).
[SUMMARY] These data indicate that GnRHa induced gonadal suppression did not affect somatic growth or IGF-1 in male rats, while suppressed gonadotropin-estrogen axis resulted in increased body weight without changes in circulating IGF-1 levels in female rats, and this effect appears to be mediated through GH. Less