Endocrine Abstracts

BackgroundIn addition to inhibiting pituitary GH secretion, somatostatin (SS) and its analogues have been shown to exert anti-proliferative effects on a variety of different cell types. The presence of receptors for SS have been demonstrated in a number of tissues but quantification of mRNA expression of the 5 subtypes of SSTR in the colon is unknown.MethodsTotal RNA was extracted from 9 paired samples of adj...

Background: Patients with acromegaly have an increased risk of colorectal neoplasia. In non-acromegalic subjects, carcinomas develop from dysplastic tubular adenomas and colonoscopic removal of these reduces the subsequent incidence of carcinoma. The frequency of such screening in acromegaly is controversial and it is uncertain which patients should be considered to be at particular increased risk. Methods: We reviewed the incidence of new colonic lesions amongst our large coh...

Background: We have previously demonstrated colonic expression of the endogenous GH secretagogue, ghrelin, but not the GHS-R, and that ghrelin exerts proliferative effects on colonic epithelial cells. However, whether these are specific to ghrelin, or which genes are affected in response is uncertain.Aims: Determine the specificity of the proliferative effects of ghrelin on colonic epithelial cells, and effects on mRNA levels of the cancer associated ge...

Background:Circulating levels of IGFBP-3 are inversely associated with the risk of developing colorectal cancers (CRC). In addition to modulating IGF bioavailability, IGFBP-3 also exerts independent pro-apoptotic effects. Furthermore, the mode of action of several apoptotic and antiproliferative agents, including vitamin D, has been shown to involve induction of IGFBP-3.Aims:To quantitate and compare IGFBP-3 ...

Introduction: The GH/IGF-I axis is implicated in colorectal cancer development. We have previously shown regional variations of the GH/IGF-I axis, and other tumour associated genes between the rectum (RS) and caecum (C). Whether variations in the GH/IGF-I axis align with differing expression patterns is unknown.Aim: To determine the association between colonic expression of the GH/IGF-I axis and that of tumour associated genes by region.<p class="abs...

Background: Vitamin D prevents proliferation, promotes differentiation and induces apoptosis of colonic cells. A reduced dietary intake is associated with an increased risk of colorectal cancer (CRC). Recently, we have shown that 25-hydroxyvitamin D-1-alpha hydroxylase (1aOHase) mRNA, which converts vitamin D to its active metabolite, is upregulated in CRC. However, this was based on small number of samples and data on vitamin D receptor (VDR) expression in CRC are inconsisten...

Background: Sporadic colorectal carcinoma (CRC) is more common on the left side of the colon. Acromegaly confers an increased risk of developing CRC but with an increase of right sided disease. IGFBP-3 both regulates tissue exposure to IGF-I and also exerts cellular IGF-l independent pro-apoptotic effects. Whether variation in regional IGFBP-3 expression in the colon may explain the observed pattern of disease in both normal and acromegalic patients is unknown.Aim: 1) To c...

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 ...

Background: Acromegalics are at increased risk of developing colorectal neoplasia with an increase of right-sided disease. Several genes are implicated in colorectal neoplasia including components of the GH/IGF-1 axis. It is unclear whether regional variations in neoplasia are explained by variations in local expression of these genes. Aims: To compare the expression of the components of the GH/IGF-1 axis and other putative genes between the left and right colon of patients wi...

Background: We have recently demonstrated universal and high levels of expression of growth hormone in the human colon, despite the absence of GHRH or its receptor. Although ghrelin, recently shown to be an additional endogenous GH secretagogue, is expressed in the human colon, little is known about its distribution within the colon or function and whether any effects are GH-dependent.Aims: To investigate the mRNA expression of ghrelin and ...