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 |
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Authors: | Rina Eshet Irit Gil-Ad Olga Apelboym Yael Segev Moshe Phillip Haim Werner |
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Affiliation: | (1) Laboratory of Endocrinology and Diabetes, Felsenstein Medical Research Center, Petah Tikva, Israel;(2) Laboratory of Neurobiology, Felsenstein Medical Research Center, Petah Tikva, Israel;(3) Institute of Endocrinology and Diabetes, Schneider Children’s Medical Center of Israel, Petah Tikva, Israel;(4) Molecular Endocrine Laboratory, Soroka Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel;(5) Department of Clinical Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel |
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Abstract: | 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. |
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Keywords: | IGF-I IGF-I receptor growth hormone somatostatin GHRH hypothalamus |
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