Differential effects of insulin and Insulin-Like Growth Factor I on the production of Plasma Steroid-Binding Globulins by Human Hepatoblastoma-Derived (Hep G2) cells
| Autor: | Michel Pugeat, C. Brébant, C Baret, J C Crave, Hervé Lejeune |
|---|---|
| Přispěvatelé: | ProdInra, Migration, Communications Cellulaires et Différenciation (CCD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA) |
| Jazyk: | angličtina |
| Rok vydání: | 1995 |
| Předmět: |
Hepatoblastoma
medicine.medical_specialty Globulin Endocrinology Diabetes and Metabolism medicine.medical_treatment [SDV]Life Sciences [q-bio] Clinical Biochemistry Biochemistry Insulin-like growth factor Endocrinology Sex hormone-binding globulin Transcortin Somatomedins Internal medicine Sex Hormone-Binding Globulin polycyclic compounds medicine Tumor Cells Cultured Humans Insulin Insulin-Like Growth Factor I reproductive and urinary physiology Pancreatic hormone biology Estradiol Biochemistry (medical) Liver Neoplasms Hep G2 Insulin-Like Growth Factor Binding Protein 1 [SDV] Life Sciences [q-bio] Steroid hormone Thyroxine biology.protein Carrier Proteins hormones hormone substitutes and hormone antagonists |
| Zdroj: | Journal of Clinical Endocrinology and Metabolism Journal of Clinical Endocrinology and Metabolism, Endocrine Society, 1995, 80 (4), pp.1283-1289 |
| ISSN: | 0021-972X 1945-7197 |
| Popis: | Changes in the plasma levels of corticosteroid-binding globulin (CBG) and sex hormone-binding globulin (SHBG) from birth to adulthood suggest that growth factors might influence clearance and/or hepatic secretion of CBG and SHBG in humans. The effects of insulin-like growth factor I (IGF-I) and insulin on CBG and SHBG synthesis by a clone of human hepatoblastoma-derived (Hep G2) cell lines were therefore investigated. The results showed that the immunoconcentrations of CBG and SHBG, as well as total protein concentration in culture medium from Hep G2 cells, were decreased by IGF-I and insulin. However, although the CBG-to-total protein ratio was decreased dose dependently by IGF-I and insulin, IGF-I and insulin did not dose-dependently decrease the SHBG-to-total protein ratio. The steady state levels of CBG and SHBG messenger RNAs (mRNAs) were reduced dose dependently by IGF-I with a half-effect at 5.4 +/- 1.9 and 4.6 +/- 1.6 nmol/L, respectively, and by insulin with a half-effect at 4.3 +/- 1.1 and 4.3 +/- 1.4 nmol/L, respectively. The maximum inhibitory effect of IGF-I on CBG mRNA level was 48 +/- 17% of control values and 60 +/- 13% for SHBG mRNA level. The changes in CBG mRNA levels were quantitatively similar to the changes in CBG immunoconcentration in the Hep G2 medium. In contrast, the inhibitory effects of insulin were only 17 +/- 8% and 31 +/- 12% of control values on CBG and SHBG mRNAs and 37 +/- 4% and 43 +/- 4% on CBG and SHBG concentrations, respectively. These results demonstrate that IGF-I reduces CBG and SHBG production by Hep G2 cells by decreasing mRNA steady state levels. The discrepancy between the inhibitory effects of insulin on CBG and SHBG mRNAs and protein secretion suggests that insulin exercises its inhibitory effects mainly on the mechanism(s) of translation and/or excretion of CBG and SHBG. The respective effects of IGF-I and insulin in the regulation of CBG and SHBG levels during fetal life and pubertal development in humans merit further study. |
| Databáze: | OpenAIRE |
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