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
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
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.
3738-3746
Richardson, Malcolm C.
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Cameron, Iain T.
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Simonis, Chantal D.
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Das, Madhab C.
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Hodge, Tessa E.
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Zhang, Junlong
68a8fa77-c5db-4b34-aa9a-fbad6860155f
Byrne, Christopher D.
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June 2005
Richardson, Malcolm C.
0a81790c-5e49-48a2-ae81-83ca287b494a
Cameron, Iain T.
f7595539-efa6-4687-b161-e1e93ff710f2
Simonis, Chantal D.
9d18e977-867b-4ef5-9d58-277b4da1b6be
Das, Madhab C.
09cffc6f-1b6a-4609-b6ac-dd884555ea9f
Hodge, Tessa E.
23a937e5-1500-4509-9372-ed5b8a794fef
Zhang, Junlong
68a8fa77-c5db-4b34-aa9a-fbad6860155f
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c
Richardson, Malcolm C., Cameron, Iain T., Simonis, Chantal D., Das, Madhab C., Hodge, Tessa E., Zhang, Junlong and Byrne, Christopher D.
(2005)
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.
Journal of Clinical Endocrinology & Metabolism, 90 (6), .
(doi:10.1210/jc.2004-2057).
Abstract
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.
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Published date: June 2005
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Local EPrints ID: 25935
URI: http://eprints.soton.ac.uk/id/eprint/25935
ISSN: 0021-972X
PURE UUID: 8ff34d36-671a-4598-ad04-335fa9d1ac82
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Date deposited: 20 Apr 2006
Last modified: 16 Mar 2024 03:07
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Author:
Malcolm C. Richardson
Author:
Chantal D. Simonis
Author:
Madhab C. Das
Author:
Tessa E. Hodge
Author:
Junlong Zhang
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