Mutations in the c-erbA beta 1 gene: do they underlie euthyroid fibromyalgia?
Fibromyalgia, a chronic condition of widespread pain, stiffness, and fatigue, has proven unresponsive to drugs, the use of which is based on the 'serotonin-deficiency hypothesis'. An alternative hypothesis-failed transcription regulation by thyroid hormone-can explain the serotonin deficiency and other objective findings and symptoms of euthyroid fibromyalgia. Virtually every feature of fibromyalgia corresponds to signs or symptoms associated with failed transcription regulation by thyroid hormone. In hypothyroid fibromyalgia, failed transcription regulation would result from thyroid-hormone deficiency. In euthyroid fibromyalgia, failed transcription regulation may result from low-affinity thyroid hormone receptors coded by a mutated c-erbA beta 1 gene, yielding partial peripheral resistance to thyroid hormone. The hypothesis of this paper is that, in euthyroid fibromyalgia, a mutant c-erbA beta 1 gene (or alternately, the c-erbA alpha 1 gene) results in low-affinity thyroid-hormone receptors that prevent normal thyroid hormone regulation of transcription. As in hypothyroidism, this would cause a shift toward alpha-adrenergic dominance and increases in both cyclic adenosine 3'-5'-phosphate phosphodiesterase and inhibitory Gi proteins. The result would be tissue-specific hypothyroid-like symptoms despite normal circulating thyroid-hormone levels.
Lowe
J C
JC
Fibromyalgia Research Foundation, Houston, TX 77277, USA. JLowe55555@aol.com
Cullum
M E
ME
Graf
L H
LH
Yellin
J
J
D000818:Animals; D005356:Fibromyalgia / Q000235:genetics* / Q000503:physiopathology; D019382:Human Growth Hormone / Q000502:physiology; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics / Q000503:physiopathology; D008954:Models, Biological; D009154:Mutation; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis* / Q000235:genetics*; D012701:Serotonin / Q000502:physiology; D013961:Thyroid Gland / Q000502:physiology* / Q000503:physiopathology*; D013963:Thyroid Hormones / Q000502:physiology*; D014158:Transcription, Genetic
D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D019382:Human Growth Hormone; D012701:Serotonin