Modulation of brain insulin-like growth factor I (IGF-I) binding sites and hypothalamic GHRH and somatostatin levels by exogenous growth hormone and IGF-I in juvenile rats.
The effect of exogenous growth hormone (GH) and insulin-like growth factor I (IGF-I) on brain IGF-I binding sites (IGF-IR), and on the levels of growth hormone-releasing hormone (GHRH) and somatostatin was studied in hypophysectomized and intact juvenile male rats. Animals were injected subcutaneously twice daily (n = 5 each) with recombinant GH (rGH) (2.5 U/kg per day) or rIGF-I (500 microg/kg per day). In the hypophysectomized rats, serum GH and IGF-I levels were markedly suppressed and IGF-I levels were partially restored by GH treatment. There was a significant increase in IGF-IR binding capacity in the IGF-I-treated hypophysectomized rats compared to the saline-treated hypophysectomized animals (150.61 +/- 45.66 vs 41.32 +/- 12.42 fmol/mg, p < 0.05) but no significant difference in IGF-IR mRNA levels. GHRH levels in the saline-treated hypophysectomized group were significantly lower than in the saline-treated intact rats (31.2 +/- 11.2 vs 140.6 +/- 48.1 pg/mg tissue, respectively, p < 0.01); no effect was induced by GH or IGF-I (37.5 +/- 26.8 and 53.8 +/- 22.5 pg/mg tissue, respectively). However, in the intact rats, GH and IGF-I injection led to a decrease in GHRH content, which was significant in the GH-treated compared to the saline-treated animals (33.1 +/- 16.2 vs 140.6 +/- 48.1 pg/mg tissue, p < 0.01). No difference was found in somatostatin levels between intact and hypophysectomized rats (631.2 +/- 81.2 and 625.0 +/- 62.5 pg/mg tissue, respectively). However, in the hypophysectomized animals, GH and IGF-I treatment induced a significant increase in somatostatin levels (1300 +/- 193.7 pg/mg tissue, p < 0.01, and 912.5 +/- 81.2 pg/mg tissue, p < 0.05, respectively). Our findings suggest that the bioavailability of exogenous IGF-I is greater than that of GH-stimulated endogenous IGF-I. Because IGF-I is a potent neurotrophic agent, this effect may have important implications for states of neurodegenerative diseases.
Eshet
Rina
R
Laboratory of Endocrinology and Diabetes, Felsenstein Medical Research Center, Petah Tikva, Israel.
Gil-Ad
Irit
I
Apelboym
Olga
O
Segev
Yael
Y
Phillip
Moshe
M
Werner
Haim
H
D000367:Age Factors; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D013006:Growth Hormone / Q000097:blood / Q000494:pharmacology*; D013007:Growth Hormone-Releasing Hormone / Q000187:drug effects / Q000378:metabolism*; D007016:Hypophysectomy; D007031:Hypothalamus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009929:Organ Size / Q000187:drug effects / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017526:Receptor, IGF Type 1 / Q000187:drug effects / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013004:Somatostatin / Q000187:drug effects / Q000378:metabolism*
D011993:Recombinant Fusion Proteins; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D017526:Receptor, IGF Type 1