Clur A
Department of Anaesthesia, University of the Witwatersrand, Johannesburg, South Africa.
Med Hypotheses. 1988 Dec;27(4):303-11. doi: 10.1016/0306-9877(88)90012-6.
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.
甲状腺功能减退和低碘摄入可能是乳腺、子宫和卵巢雌激素依赖性肿瘤的重要病因。它们是可预防的风险因素。补充碘有望在未来几代人中降低这些癌症的发病率。本文作者提出，雌激素受体疏水雌激素结合位点中的酪氨酰残基在翻译后被过氧化物酶活性修饰为单碘酪氨酸，进而生成3,3'-二碘甲状腺原氨酸单胺（T2）。他之前曾提出，各种单胺受体也是基于T2的。这些受体的密度在甲状腺功能减退时会增加，它们在下丘脑 - 垂体轴的多个部位控制催乳素和其他激素（包括褪黑素）的释放。褪黑素是血清素的代谢产物，因此褪黑素受体也可能基于T2或反式三碘甲状腺原氨酸（rT3）。这些因素在乳腺癌的病因中可能很重要，因为高催乳素和褪黑素水平可能具有保护作用。甲状腺功能减退时雌激素受体密度可能会增加，某些单胺受体密度也是如此。这会放大甲状腺功能减退时高循环雌激素水平的影响，并且可能有助于解释为什么甲状腺功能减退和低碘摄入是乳腺癌、子宫癌和卵巢癌的风险因素。
