Endocrine Abstracts

Introduction: Somatotroph adenomas are GH producing pituitary adenomas. There are two main types based on granulation pattern: sparsely and densely granulated. Each type also has their own fibrous body pattern. Sparsely granulated (SG) have a ‘dot-like’ fibrous body pattern and the densely granulated (DG) have a ‘perinuclear’ fibrous body pattern. The fibrous bodies are mainly composed of keratin 8. Previous microarray analysis revealed six differentially expressed cytoskeleton specific genes (ANLN, DSP, SDC4, DSG2, IQGAP2 and TAGLN) that may be responsible for the different fibrous body patterns.

Aims/objectives: To validate the genes of interest using RT-qPCR in human samples and to induce fibrous bodies in the GH3 rat somatomammotroph cell line using drugs.

Methods: RT-qPCR was performed for the validation of the six genes using human sparsely, densely and normal pituitaries. GH3 cells were treated with the drugs Nocodazole or Griseofulvin for 72 h and immunocytochemistry (ICC) was subsequently performed for cytokeratin 8, actin or tubulin.

Results: RT-qPCR revealed a significant decrease in expression for DSP, SDC4, DSG2 and IQGAP2 when comparing both SG and DG to normal pituitaries. When comparing SG to DG, IQGAP2 was significantly decreased. From the immunocytochemistry, Nocodazole-treated cytokeratin-8 stained cells showed a ‘dot-like’ pattern similar to that observed in human SG tumours. All other treated cells produced multiple ‘dot-like’ structures.

Conclusion: We have demonstrated a differential expression of several cytoskeleton specific genes between tumour and normal pituitaries and identified differential expression of one of the genes when comparing sparsely and densely granulated adenomas. The cytoskeleton may play a role in the development of fibrous bodies. Fibrous body-like structures can be induced by the drugs we applied. The role of fibrous bodies in the clinical behaviour of somatotroph adenoma requires further studies.