guanosine-triphosphate and Graves-Disease

The characterisation of receptor sites of hormones to various tissues in vivo and in vitro have introduced new insights for the evaluation of pathogenic mechanisms involved in endocrine and metabolic human diseases. Disorders at the receptor level are characterized by changes in the number of receptor sites, the affinity of the hormone to its specific receptors or by generation of anti-receptor antibodies, which impair hormone binding procedures or post-receptor metabolism. Altered receptor physiology may be of an important value as well for diagnosis and treatment of endocrine, metabolic and neoplastic diseases as for the understanding of their pathogenetic mechanisms.

Topics: Acanthosis Nigricans; Adenosine Triphosphate; Adenylyl Cyclases; Antibodies; Binding, Competitive; Cyclic AMP; Diabetes Complications; Endocrine System Diseases; Enzyme Activation; Graves Disease; Guanosine Triphosphate; Humans; Hypercholesterolemia; Insulin; Insulin Resistance; Lipoproteins, LDL; Metabolic Diseases; Myasthenia Gravis; Obesity; Receptors, Androgen; Receptors, Cell Surface; Receptors, Neurotransmitter

The purpose of this study was to develop and validate a sensitive method for evaluating adenylate cyclase stimulation by thyroid-stimulating antibodies (TSAb), based on the measurement of thyroid membrane adenylate cyclase activity in the presence of a non-hydrolyzable GTP analogue, guanyl-5'-yl imidodiphosphate (Gpp(NH)p). The addition of Gpp(NH)p (10(-5)M) produced a 10-fold increase of the sensitivity of the system for both TSH and TSAb. Immunoglobulin G preparations from sera of 30 patients with Graves' disease were tested for the adenylate cyclase stimulation either in the presence or in the absence of Gpp(NH)p: a significant stimulation was observed in 27/30 patients when the GTP analogue was added to the system, while only 20/30 patients were positive in the absence of the nucleotide. The advantage of Gpp(NH)p addition was also evident in a large series which included 57 patients with Graves' disease, 15 with Hashimoto's thyroiditis or primary myxoedema and 22 normal subjects. In fact, 88% of patients with Graves' disease resulted positive, while no significant stimulation was elicited by Hashimoto's thyroiditis, primary myxoedema and by normal immunoglobulins. The sensitivity achieved in our system which employs thyroid plasma membranes was similar to that obtained by other investigators with the use of thyroid slices or thyroid cells in primary culture. Furthermore, methods based on thyroid plasma membranes are supposed to have a better reproducibility, since the same tissue preparation, if appropriately stored, may be used in several different tests.

Topics: Adenylyl Cyclases; Cell Membrane; Graves Disease; Guanosine Triphosphate; Guanylyl Imidodiphosphate; Humans; Immunoglobulin G; Immunoglobulins; Myxedema; Thyroid Gland; Thyroiditis, Autoimmune; Thyrotropin