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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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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 µg/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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Authors and Affiliations

  1. Laboratory of Endocrinology and Diabetes, Felsenstein Medical Research Center, Petah Tikva, Israel

    Rina Eshet, Olga Apelboym & Moshe Phillip

  2. Laboratory of Neurobiology, Felsenstein Medical Research Center, Petah Tikva, Israel

    Irit Gil-Ad

  3. Institute of Endocrinology and Diabetes, Schneider Children’s Medical Center of Israel, Petah Tikva, Israel

    Rina Eshet & Moshe Phillip

  4. Molecular Endocrine Laboratory, Soroka Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel

    Yael Segev

  5. Department of Clinical Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Haim Werner

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  1. Rina Eshet
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Correspondence to Haim Werner.

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Eshet, R., Gil-Ad, I., Apelboym, O. et al. 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. J Mol Neurosci 22, 179–188 (2004). https://doi.org/10.1385/JMN:22:3:179

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