Room 133 (Moscone Center)
Poster Board MON-112
Using transgenic mice with expression of Gsα* induced by tetracycline specifically in somatotrophs (GH-Cre/Rosa26-rtTA/TetO- Gsα*) we have investigated the effects of either constant (CON) or post-weaning (PW) chronic Gsα activation. Surprisingly, CON or PW induction of Gsα* did not lead to increased growth in 6-week old animals, which had normal pituitaries and no increase in pituitary GH content. By 100-days of age, however, induction of Gsα* led to an increased rate of growth, which was more pronounced in CON than PW mice. Pituitary morphology at this age was normal, there was no obvious somatotroph hyperplasia and GH content was not markedly increased. Analysis of somatostatin (SST)-null mice with induction of Gsα* demonstrated that SST was not responsible for the lack of effect on somatotroph hyperplasia or growth rate of young animals. At 5-6 months of age all mice with induction of Gsα* developed nodes of somatotroph hyperplasia, which lead to the development of pituitary tumours without increased somatotroph proliferation in non-tumourous regions of the gland. These hyperplastic nodes and tumours consist of proliferating somatotrophs, with a reduction in reticulin staining. Increased platelet derived growth factor receptor-beta staining in cells lining capillaries and in the parenchyma surrounding hyperplastic somatotrophs, suggests induction of pericytes within tumourous tissue.
These results suggest that a requirement for signalling in addition to Gsα activation or inhibition with factors such as phosphodiesterases prevents increased somatotroph proliferation and GH expression in this model. In older adult animals there is a change in physiology or somatotroph biology to permit hyperplasia leading to tumour formation. This mouse model, with reversible induction of a tumourigenic factor, is an excellent model for the study of somatotroph biology and tumourigenesis, including the factors controlling their formation, maintenance and persistence.
Nothing to Disclose: LC, PS, CL, PEM, PRL
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