Endocrine Abstracts (2001) 2 P61

MIF (Macrophage Migration Inhibitory Factor) is over-expressed in the nucleus of pituitary adenoma cells

ME Pyle1, S Jordan1, M Gueorguiev1, A Meinhardt2, C Metz3, R Bucala3, M Korbonits1 & AB Grossman1

1Department of Endocrinology, St Bartholomew's Hospital, London, EC1A 7BE, UK; 2Department of Anatomy and Cell Biology, Philipps University of Marburg, Germany; 3Picower Institute, New York, USA.

MIF can override the anti-inflammatory actions of glucocorticoids during immune response, and thus is an important pro-inflammatory factor. The presence of MIF in the cytoplasm of adenomatous cells of the anterior pituitary has been described, and high levels of MIF in other rapidly-proliferating tissues have been demonstrated. It is hypothesized that MIF release from these cells is influenced by the hypothalamo-pituitary-adrenal axis, and that ACTH and MIF are released simultaneously to exert counter-regulatory effects on cortisol. However, another intracellular role for MIF has been suggested since it was shown that MIF exerts an effect on the inhibitory cell cycle control protein p27 through interaction with Jab1.

We studied MIF expression in pituitary adenomas and normal pituitary, and related this to expression of p27, Jab1 and Ki-67 (the indicator of proliferation), using immunohistochemical and RT-PCR techniques. Our results showed that MIF was predominantly expressed in cell nuclei, and that there is increased expression of MIF in the nuclei of pituitary adenomas compared to normal pituitary (p=0.0067); there was no statistically significant difference in nuclear MIF expression between different adenoma types (p=0.06). Statistically significant correlations between nuclear Jab1 and MIF expression in ACTH-secreting tumours (p=0.01), and nuclear MIF and Ki-67 expression in GH-secreting tumours (p=0.017) was demonstrated. There was no difference in cytoplasmic MIF expression between adenomatous and normal pituitary samples. MIF mRNA was demonstrated to be equally present in all tumorous and normal samples. These results support the theory that there is increased nuclear MIF expression in rapidly proliferating tissues. In conclusion, MIF expression in pituitary adenomas is greater than in normal pituitary tissue; therefore it is likely to play a role in control of the cell cycle. We speculate that this increased expression is a consequence of tumour formation, and may be an attempt to block Jab1 thus controlling proliferation.

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