Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2004) 8 P74

SFE2004 Poster Presentations Reproduction (8 abstracts)

Effect of gonadotrophin and insulin on the balance of sterol regulatory element-binding protein(SREBP) isoforms in human granulosa cells

MC Richardson , IT Cameron , CD Simonis , MC Das , TE Hodge , J Zhang & CD Byrne


Maternal, fetal and neonatal physiology, University of Southampton.


Clinical insulin resistance, concomitant with higher circulating insulin, is implicated in the pathogenesis of polycystic ovary syndrome (PCOS) in which there is abnormal lipid metabolism with changes in ovarian hormone production. SREBPs are key transcriptional regulators of lipid biosynthesis and therefore may be involved in changes occurring in PCOS. We have examined whether insulin and gonadotrophin regulate SREBPs.

Local ethical approval was granted for preparing granulosa cells (GC) from follicular aspirates obtained during egg collection for IVF. After removal of white cells, GC were put into culture in the presence of serum. Following a period in serum-free medium, GC were exposed to hCG, insulin or both hormones for 16h. Culture medium was collected and cellular RNA extracted for the measurement of mRNAs by a quantitative, competitive RT-PCR method.

Addition of hCG strongly stimulated progesterone production (7.03-fold, P<0.001 vs control), while insulin increased lactate production (1.38-fold, P<0.001 vs control) and decreased IGFBP-1 output by 85% (P<0.001, hCG/insulin vs hCG alone). While there was no significant effect of either hormone on induction of mRNA for SREBP-1a, there were increases in mRNA for SREBP-1c with insulin alone (6.3-fold), hCG alone (10.4-fold) and in combination (15.2-fold; P<0.01 for all comparisons vs control). No consistent effect of either hormone on SREBP-2 expression was observed. Expression of representative target genes for SREBP was also increased by hCG and insulin (fatty acid synthase, 24-fold and 19-fold respectively; HMGCoA reductase, 7.5-fold and 6.4-fold respectively).

We show for the first time how SREBP isoforms are separately regulated in GC. Both hCG and insulin cause a switch towards expression of the SREBP-1c isoform which would be expected to have a predominant effect on fatty acid synthesis. We suggest that insulin causes alteration in the expression of a key regulator of lipid metabolism that may affect the PCOS phenotype in vivo

Volume 8

195th Meeting of the Society for Endocrinology joint with Diabetes UK and the Growth Factor Group

Society for Endocrinology 

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