Increased creatine kinase activity in pituitary tumours of rat and man

Abstract

The demonstration that phosphocreatine is used as an energy source by rat PRL-secreting pituitary tumours prompted the study of the enzyme creatine kinase in both rat and human pituitary tumours. Rats treated with diethylstilbestrol developed greatly enlarged pituitaries and hyperprolactinaemia. Total creatine kinase was significantly increased and fractionation on diethylaminoethyl Sephadex showed that the 'brain' form was increased, whereas the 'muscle' and mitochondrial forms showed no change. Exposure to large concentrations of oestradiol caused similar changes in creatine kinase which increased over a period of 25 weeks. The total creatine kinase content of a series of human pituitary tumours was highly variable, but the mean value of 183 +/- 46 (SEM) units per gram protein was significantly higher than the mean for normal pituitary tissues (28.4 +/- 2.9). The brain:muscle isozyme ratio was measured in six human PRL-secreting tumours with a mean of 3.47 +/- 0.73, significantly higher than in 'non-functional' tumours (1.57 +/- 0.29) or normal tissue (1.77 +/- 0.28). Three of four GH-secreting tumours had a ratio below 0.6. The highest ratio found (8.66) was in an ACTH-secreting tumour. Previous reports have shown that oestradiol rapidly induces brain creatine kinase in oestrogen responsive tissues. This is not the case with the rat pituitary gland or oestrogen responsive human tumour cells in culture. Chronic oestrogen treatment, however, does increase creatine kinase in the proliferating gland and many human pituitary tumours have increased enzyme activity. These results suggest that the phosphocreatine/ATP system and in particular the brain isozyme of creatine kinase are of particular importance in lactotropes.