Endocrine Abstracts

Apoptosis or programmed cell death, is a principal mechanism controlling the physiological development of most living organs by removing unwanted cells without inducing an inflammatory response. It is known that in autoimmune thyroid conditions such as Graves' disease, thyroid cells die by apoptosis. Dysregulation of pro- and anti-apoptotic gene expression may be critical to the induction of the destructive process via the activation of a sequence of caspases (proteases).

Conventionally, apoptosis occurs via 2 main pathways: the Intrinsic pathway mediated by mitochondria, resulting in the activation of caspase 9 while the Extrinsic pathway is mediated by the activation of death receptors (Fas and TNFR) and involves the activation of caspase 8. Both pathways converge with the activation of effector caspases. Tracing the pathways that cause cell death should enable the development of novel reagents for disease prevention. It could also lead to the treatment and prevention of not only thyroid autoimmune conditions but provide insight into the pathological mechanisms in other autoimmune diseases, such as Insulin Dependent Diabetes Mellitus. By applying gene array technology both pathways can be examined simultaneously.

RNA was extracted from enriched thyrocyte preparations from 6 thyroids from patients with Graves' disease and from 6 with Multinodular goitre (control group). This was transcribed into cDNA and hybridised to 96 apoptotic gene specific cDNA fragments printed onto a nylon membrane. The data were analysed using Scanalyze software.

In samples from Multinodular goitre the pattern of apoptotic gene expression was more consistent than that in Graves' disease. In both thyroid conditions, TNFR2 expression was strongly expressed. Caspase 14 and MCL-1, RIP, TRAF1 and BAK apoptosis-related genes were found increased in Graves' thyroids while caspase 8 or 9 were not clearly expressed.

Our preliminary results show that there may be a non-conventional pathway of apoptotic activation in Graves' disease.