Di-iodothyronine as part of the oestradiol and catechol oestrogen receptor--the role of iodine, thyroid hormones and melatonin in the aetiology of breast cancer.
Hypothyroidism and low iodine intake may be important aetiological factors in oestrogen dependent tumours of the breast, uterus and ovary. They are preventable risk factors. Iodine supplementation will hopefully lead to a decreased incidence of these cancers in future generations. The present author proposes that the tyrosyl residue in the hydrophobic oestrogen binding site of the oestrogen receptor is post translationally modified to monoiodotyrosine and hence 3,3' di-iodothyronine monoamine (T2) by peroxidase activity. He has previously proposed that various monoamine receptors are also T2 based. The densities of these receptors are increased in hypothyroidism and they exert control over release of prolactin and other hormones, including melatonin at multiple sites in the hypothalamic--pituitary axis. Melatonin is a metabolite of serotonin and hence melatonin receptors may be T2 or rT3 based as well. These factors could be significant in the aetiology of breast cancer as high prolactin and melatonin levels may be protective. Oestrogen receptor density may be increased in hypothyroidism as is certain monoamine receptor density. This would amplify the effect of high circulation oestrogen levels in hypothyroidism and may help explain why hypothyroidism and low iodine intake are risk factors for breast, uterine and ovarian cancer.
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Department of Anaesthesia, University of the Witwatersrand, Johannesburg, South Africa.
D001943:Breast Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D004104:Diiodothyronines / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000150:complications; D007455:Iodine / Q000008:administration & dosage; D008550:Melatonin / Q000378:metabolism; D008954:Models, Biological; D011388:Prolactin / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D013970:Thyronines / Q000378:metabolism*
D004104:Diiodothyronines; D011960:Receptors, Estrogen; D013970:Thyronines; C030629:3,3'-diiodothyronine; D011388:Prolactin; D007455:Iodine; D008550:Melatonin; D004298:Dopamine