Insulin and Human Chorionic Gonadotropin Cause a Shift in the Balance of Sterol Regulatory Element-Binding Protein (SREBP) Isoforms Toward the SREBP-1c Isoform in Cultures of Human Granulosa Cells
| Autor: | Junlong Zhang, Chantal D. Simonis, Christopher D. Byrne, Tessa E. Hodge, M. C. Richardson, Iain T. Cameron, Madhab C. Das |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
endocrine system
medicine.medical_specialty DNA Complementary medicine.drug_class Endocrinology Diabetes and Metabolism Granulosa cell medicine.medical_treatment Clinical Biochemistry Fertilization in Vitro Fatty Acids Nonesterified Chorionic Gonadotropin Biochemistry Endocrinology Insulin resistance Lipid biosynthesis Internal medicine medicine Humans Insulin RNA Messenger Cells Cultured Progesterone DNA Primers Granulosa Cells biology Biochemistry (medical) medicine.disease DNA-Binding Proteins Insulin-Like Growth Factor Binding Protein 1 Fatty acid synthase CCAAT-Enhancer-Binding Proteins biology.protein Sterol Regulatory Element Binding Protein 1 Female Sterol regulatory element-binding protein 2 Fatty Acid Synthases Gonadotropin Sterol Regulatory Element Binding Protein 2 Transcription Factors |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 90:3738-3746 |
| ISSN: | 1945-7197 0021-972X |
| Popis: | The isoforms of sterol regulatory element-binding proteins (SREBP) (1a, 1c, and 2) are key transcriptional regulators of lipid biosynthesis. We examined their regulation by gonadotropin and insulin in human granulosa cells. After removal of leukocytes, granulosa cells were exposed to hormonal additions for 16 h starting on d 2 of culture. Progesterone, lactate, and IGF binding protein-1 were measured in culture medium and cellular mRNA measured by competitive RT-PCR. Addition of human chorionic gonadotropin (hCG) (100 ng/ml) stimulated progesterone production (7.0-fold, P < 0.001 vs. control), whereas lactate was increased by hCG (1.6-fold, P < 0.001) and insulin (1.4-fold, P < 0.001; 1000 ng/ml). Insulin decreased IGF binding protein-1 production by 85% (P < 0.001). There were no significant effects on the expression of SREBP-1a but significant increases in mRNA for SREBP-1c with insulin (6.3-fold), hCG (10.4-fold) and in combination (15.2-fold; P < 0.01 for all comparisons). No consistent effects on SREBP-2 were observed. The expression of mRNA for fatty acid synthase, a target gene for SREBP-1c, was increased by hCG (24-fold, P = 0.006) and insulin (19-fold, P = 0.024), which also increased the level of cellular, total fatty acid (1.34-fold; P = 0.03). Thus, hCG and insulin cause a switch toward expression of the SREBP-1c isoform with consequent effects on fatty acid synthesis. We suggest that high circulating insulin, associated with clinically defined insulin resistance, may up-regulate SREBP-1c expression in the ovary. |
| Databáze: | OpenAIRE |
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