Gonadal suppression by a GnRH analogue does not alter somatic growth in rats with complete GH deficiency.
Sexual dimorphism of somatic growth in rats appears to reflect differing actions of sex steroids. However, mechanisms of gonadal steroid effects on the somatotropic axis are incompletely understood. To evaluate whether GH is involved in the effects of long-term gonadal suppression on somatic growth in rats, a GnRH agonistic analogue (GnRHa) was administered to normal Sprague-Dawley rats (controls) and to a strain of rats with complete growth hormone deficiency (GHD; n=4-6 in each group). Subcutaneous injection of GnRHa (2 mg/kg) or saline were given within 48 h after birth and repeated every 3 weeks. GnRHa treatment significantly reduced serum gonadal steroid levels in rats of both sexes with small testes in males and impaired development of internal genitalia in females. GnRHa-treated control females became significantly heavier (P<0.01 ANOVA for repeated measures) than saline-treated rats beginning at 8 weeks. However, female GHD rats with GnRHa treatment did not differ in body weight from rats receiving saline. In male rats, GnRHa treatment did not change body weight in either control or GHD rats. Serum IGF-I concentrations did not differ between treatment groups in GHD and control rats of either sex. Hepatic GH binding was reduced significantly by GnRHa treatment in female control rats (P<0.01), but not in female GHD rats. These data suggest that sexual dimorphism in body size and its modulation by estrogens are independent of circulating IGF-I levels suggesting non-endocrine IGF-I-mediated mechanisms, and that GH-induced somatic growth is modulated by estrogens, but not androgens, in rats.
Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. eogawa@ped.med.tohoku.ac.jp
E
E
Ogawa
B H
BH
Breier
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I
Fujiwara
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K
Iinuma
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D005835:Genitalia / Q000187:drug effects / Q000254:growth & development; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists* / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013006:Growth Hormone / Q000172:deficiency* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics
D007987:Gonadotropin-Releasing Hormone; C083781:LHRH, Ala(6)-Gly(10)-ethylamide-; D013006:Growth Hormone