Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2003) 5 P151

BES2003 Poster Presentations Endocrine Tumours and Neoplasia (47 abstracts)

IGF-I inhibits COX-2 function in primary colonic biopsies of patients with acromegaly

PA Kelly 1 , I Vojnovic 2 , PD Fairclough 3 , T Warner 2 , SA Bustin 4 & PJ Jenkins 1


1Department of Endocrinology, Section of Endocrine Oncology, Bart's and The London, Queen Mary's School of Medicine and Dentistry, University of London, London, UK; 2William Harvey Research Institute, Charterhouse Square, Bart's and The London, Queen Mary's School of Medicine and Dentistry, University of London, London, UK; 3Department of Gastroenterology, Bart's and The London NHS Trust, West Smithfield, London, UK; 4Department of Academic Surgery, Bart's and The London, Queen Mary's School of Medicine and Dentistry, University of London, London, UK.


Introduction: Cyclooxygenase-2 (COX-2), an inducible enzyme in prostaglandin synthesis, plays a major role in the pathogenesis of sporadic colorectal carcinoma (CRC). COX-2 inhibitors reduce the mortality from sporadic CRC. Acromegaly is associated with an increased risk of CRC, with a preponderance of right sided disease, but COX-2 protein is reduced or absent in acromegalic normal and malignant colonic mucosa. The mechanisms responsible for this are unknown.
Aims: (i) To determine the effect of IGF-I on COX-2 function in primary colonic biopsies from patients with and without acromegaly, and (ii) to determine any regional differences within the colon.
Methods: Ethics committee approval and informed consent were gained. 7 acromegalic and 3 normal patients were colonoscoped. Patients with inflammation or neoplasia were excluded. Pinch biopsies (approx 5-10mg) were taken from the caecum and rectum, divided and cultured in serum free media plus/minus IGF-I 20ng/ml at 37degC in 5%CO2 for 24h. At 24h media was collected and replaced with fresh media plus/minus IGF-I plus 30nM arachidonic acid for 1h. Viability was assessed using the MTT assay. COX-2 function was assessed by RIA for prostaglandin E2.
Results: IGF-I resulted in a fall in PgE2 production by acromegalic caecal biopsies compared to media only (median concentration 2.93 vs 1.73ng/ml respectively; p<0.02). A similar fall occurred after arachidonate addback (1.69 vs 0.77ng/ml). 5/7 rectal biopsies followed this trend. Similarly, all 3 caecal biopsies from normal subjects showed a fall in PgE2 production in response to IGF-I, but 2/3 rectal biopsies showed increased PgE2 with IGF-I. The biopsies showed no fall in mitochondrial activity for >48 hours.
Conclusions: The demonstration that IGF-I reduces COX-2 activity provides an explanation for our previous finding of reduced COX-2 protein in both normal and malignant colonic epithelium from patients with acromegaly. The tumorigenic pathway responsible for the increased cancer risk in acromegaly despite this redundancy of COX-2 remains to be determined.

Volume 5

22nd Joint Meeting of the British Endocrine Societies

British Endocrine Societies 

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