AKP健食天


Thyroid: Therapies, Confusion, and Fraud by Raymond Peat

甲状腺:治疗、混淆和欺骗

I. Respiratory-metabolic defect

呼吸代谢缺陷

II. 50 years of commercially motivated fraud

50年的商业欺诈

III. Tests and the “free hormone hypothesis”

测试和“游离激素假说”

IV. Events in the tissues

组织中的事件

V. Therapies

治疗方法

VI. Diagnosis

诊断

I. Respiratory defect

呼吸代谢缺陷

Broda Barnes, more than 60 years ago, summed up the major effects of hypothyroidism on health very neatly when he pointed out that if hypothyroid people don't die young from infectious diseases, such as tuberculosis, they die a little later from cancer or heart disease. He did his PhD research at the University of Chicago, just a few years after Otto Warburg, in Germany, had demonstrated the role of a “respiratory defect” in cancer. At the time Barnes was doing his research, hypothyroidism was diagnosed on the basis of a low basal metabolic rate, meaning that only a small amount of oxygen was needed to sustain life. This deficiency of oxygen consumption involved the same enzyme system that Warburg was studying in cancer cells.

60多年前,布罗达·巴恩斯(Broda Barnes)很好地总结了甲状腺机能减退对健康的主要影响。他指出,如果甲状腺机能减退的人不是死于肺结核等传染病,而是死于癌症或心脏病,时间稍晚一些。他在芝加哥大学(University of Chicago)完成了博士研究,就在几年前,德国的奥托•沃伯格(Otto Warburg)证明了“呼吸缺陷”在癌症中的作用。在巴恩斯做研究的时候,甲状腺功能减退症被诊断为基础代谢率低,这意味着维持生命只需要少量的氧气。这种耗氧不足涉及的酶系统与瓦伯格在癌细胞中研究的相同。

Barnes experimented on rabbits, and found that when their thyroid glands were removed, they developed atherosclerosis, just as hypothyroid people did. By the mid-1930s, it was generally known that hypothyroidism causes the cholesterol level in the blood to increase; hypercholesterolemia was a diagnostic sign of hypothyroidism. Administering a thyroid supplement, blood cholesterol came down to normal exactly as the basal metabolic rate came up to the normal rate. The biology of atherosclerotic heart disease was basically solved before the second world war.

巴恩斯在兔子身上做实验,发现当它们的甲状腺被切除后,它们就会出现动脉粥样硬化,就像甲状腺功能减退的人一样。到20世纪30年代中期,人们普遍认为甲状腺机能减退会导致血液中胆固醇水平升高;高胆固醇血症是甲状腺机能减退的诊断征象。服用甲状腺补充剂后,血液胆固醇降至正常水平与基础代谢率升至正常水平完全一致。动脉粥样硬化性心脏病的生物学在第二次世界大战之前就基本解决了。

Many other diseases are now known to be caused by respiratory defects. Inflammation, stress, immunodeficiency, autoimmunity, developmental and degenerative diseases, and aging, all involve significantly abnormal oxidative processes. Just brief oxygen deprivation triggers processes that lead to lipid peroxidation, producing a chain of other oxidative reactions when oxygen is restored. The only effective way to stop lipid peroxidation is to restore normal respiration.

现在已知的许多其他疾病都是由呼吸系统缺陷引起的。炎症、应激、免疫缺陷、自身免疫、发育和退行性疾病以及衰老,都涉及明显异常的氧化过程。仅仅是短暂的缺氧就会触发导致脂质过氧化的过程,当氧气恢复时,就会产生一系列其他的氧化反应。阻止脂质过氧化的唯一有效方法是恢复正常的呼吸。

Now that dozens of diseases are known to involve defective respiration, the idea of thyroid's extremely broad range of actions is becoming easier to accept.

现在已知有几十种疾病都与呼吸缺陷有关,甲状腺作用范围极广的观点正变得更容易被接受。

II. 50 years of fraud

50年的欺诈

Until the second world war, hypothyroidism was diagnosed on the basis of BMR (basal metabolic rate) and a large group of signs and symptoms. In the late 1940s, promotion of the (biologically inappropriate) PBI (protein-bound iodine) blood test in the U.S. led to the concept that only 5% of the population were hypothyroid, and that the 40% identified by “obsolete” methods were either normal, or suffered from other problems such as sloth and gluttony, or “genetic susceptibility” to disease. During the same period, thyroxine became available, and in healthy young men it acted “like the thyroid hormone.” Older practitioners recognized that it was not metabolically the same as the traditional thyroid substance, especially for women and seriously hypothyroid patients, but marketing, and its influence on medical education, led to the false idea that the standard Armour thyroid USP wasn't properly standardized, and that certain thyroxine products were; despite the fact that both of these were shown to be false.

直到第二次世界大战,甲状腺机能减退的诊断是基于基础代谢率(BMR)和大量的体征和症状。在1940年代末、促销(生物不合适)的PBI(蛋白结合的碘)血液检测在美国导致的概念,只有5%的人口是甲状腺,和40%的被“淘汰”方法要么是正常的,或遭受其他问题,如懒惰和贪婪,或对疾病的“遗传易感性”在同一时期,甲状腺素开始出现,在健康的年轻男性中,它的作用“就像甲状腺激素”。年长的从业人员认识到,它在代谢方面与传统的甲状腺物质不同,尤其是对于女性和严重甲状腺功能减退的患者,但市场营销及其对医学教育的影响,导致了错误的想法,即标准甲状甲状腺USP没有适当地标准化,某些甲状腺素产品;尽管事实证明这两者都是错误的。

By the 1960s, the PBI test was proven to be irrelevant to the diagnosis of hypothyroidism, but the doctrine of 5% hypothyroidism in the populaton became the basis for establishing the norms for biologically meaningful tests when they were introduced.

到20世纪60年代,PBI测试被证明与甲状腺功能减退症的诊断无关,但当它被引入时,人口中5%甲状腺功能减退症的理论成为建立有生物学意义的测试规范的基础。

Meanwhile, the practice of measuring serum iodine, and equating it with “thyroxine the thyroid hormone,” led to the practice of examining only the iodine content of the putative glandular material that was offered for sale as thyroid USP. This led to the substitution of materials such as iodinated casein for desiccated thyroid in the products sold as thyroid USP. The US FDA refused to take action, because they held that a material's iodine content was enough to identify it as “thyroid USP.” In this culture of misunderstanding and misrepresentation, the mistaken idea of hypothyroidism's low incidence in the population led to the acceptance of dangerously high TSH (thyroid stimulating hormone) activity as “normal.” Just as excessive FSH (follicle stimulating hormone) has been shown to have a role in ovarian cancer, excessive stimulation by TSH produces disorganization in the thyroid gland.

同时,测量血清碘的做法,并将其等同于“甲状腺激素甲状腺素”,导致了只检查假定的腺物质的碘含量的做法,作为甲状腺USP出售。这导致在作为甲状腺USP销售的产品中,碘化酪蛋白等材料替代了脱水甲状腺。美国食品和药物管理局拒绝采取行动,因为他们认为一种材料的碘含量足以确定其为“甲状腺USP”。在这种误解和误读的文化中,甲状腺机能减退症在人群中发病率低的错误观念导致人们将危险的高TSH(甲状腺刺激激素)活性视为“正常”。正如过量的卵泡刺激素(FSH)已被证明在卵巢癌中有作用一样,TSH的过度刺激会导致甲状腺紊乱。

III. Tests & the “free hormone hypothesis”

检验/游离激素假说

After radioactive iodine became available, many physicians would administer a dose, and then scan the body with a Geiger counter, to see if it was being concentrated in the thyroid gland. If a person had been eating iodine-rich food (and iodine was used in bread as a preservative/dough condition, and was present in other foods as an accidental contaminant), they would already be over saturated with iodine, and the gland would fail to concentrate the iodine. The test can find some types of metastatic thyroid cancer, but the test generally wasn't used for that purpose. Another expensive and entertaining test has been the thyrotropin release hormone (TRH) test, to see if the pituitary responds to it by increasing TSH production. A recent study concluded that “TRH test gives many misleading results and has an elevated cost/benefit ratio as compared with the characteristic combination of low thyroxinemia and non-elevated TSH.” (Bakiri, Ann. Endocr (Paris) 1999), but the technological drama, cost, and danger (Dokmetas, et al., J Endocrinol Invest 1999 Oct; 22(9): 698-700) of this test is going to make it stay popular for a long time. If the special value of the test is to diagnose a pituitary abnormality, it seems intuitively obvious that overstimulating the pituitary might not be a good idea (e.g., it could cause a tumor to grow).

在有了放射性碘之后,许多医生会给一个剂量,然后用盖革计数器扫描身体,看看它是否集中在甲状腺。如果一个人吃了富含碘的食物(面包中含有碘作为防腐剂或面团,其他食物中也含有碘作为一种意外污染物),那么这些食物中的碘就已经过度饱和,腺体就无法集中碘。该测试可以发现某些类型的转移性甲状腺癌,但通常不会用于这一目的。另一项昂贵而有趣的测试是促甲状腺激素释放激素(TRH)测试,以观察垂体是否通过增加促甲状腺激素的分泌来对此做出反应。最近的一项研究得出结论:“TRH试验给出了许多误导性的结果,与低甲状腺素血症和TSH不升高的特征性组合相比,TRH试验的成本/效益比更高。”(Bakiri,安。但技术的戏剧性、成本和危险(Dokmetas等,J Endocrinol Invest 1999年10月;22(9): 698-700)这个测试将使它保持流行很长一段时间。如果这项检测的特殊价值是诊断脑垂体异常,那么过度刺激脑垂体可能不是一个好主意(例如,它可能导致肿瘤生长)。

Everything else being equal, as they say, looking at the amount of thyroxine and TSH in the blood can be informative. The problem is that it's just a matter of faith that “everything else” is going to be equal. The exceptions to the “rule” regarding normal ranges for thyroxine and TSH have formed the basis for some theories about “the genetics of thyroid resistance,” but others have pointed out that, when a few other things are taken into account, abnormal numbers for T4, T3, TSH, can be variously explained.

正如他们所说,在其他条件相同的情况下,观察血液中甲状腺素和TSH的含量可以提供一些信息。问题是,这只是一个信念的问题,“其他一切”将是平等的。甲状腺素和TSH正常范围的“规则”的例外构成了一些“甲状腺抵抗遗传学”理论的基础,但也有人指出,考虑到其他一些因素,T4、T3和TSH的异常数量可以有多种解释。

The actual quantity of T3, the active thyroid hormone, in the blood can be measured with reasonable accuracy (using radioimmunoassay, RIA), and this single test corresponds better to the metabolic rate and other meaningful biological responses than other standard tests do. But still, this is only a statistical correspondence, and it doesn't indicate that any particular number is right for a particular individual.

血液中活性甲状腺激素T3的实际含量可以以合理的准确性测量(使用放射免疫分析法,RIA),而且这个单一的测试比其他标准测试更能反映代谢率和其他有意义的生物反应。但是,这只是一种统计对应,并不能表明任何特定的数字对某个特定的人来说是正确的。

Sometimes, a test called the RT3U, or resin T3 uptake, is used, along with a measurement of thyroxine. A certain amount of radioactive T3 is added to a sample of serum, and then an adsorbent material is exposed to the mixture of serum and radioactive T3. The amount of radioactivity that sticks to the resin is called the T3 uptake. The lab report then gives a number called T7, or free thyroxine index. The closer this procedure is examined, the sillier it looks, and it looks pretty silly on its face.. The idea that the added radioactive T3 that sticks to a piece of resin will correspond to “free thyroxine,” is in itself odd, but the really interesting question is, what do they mean by “free thyroxine”? Thyroxine is a fairly hydrophobic (insoluble in water) substance, that will associate with proteins, cells, and lipoproteins in the blood, rather than dissolving in the water. Although the Merck Index describes it as “insoluble in water,” it does contain some polar groups that, in the right (industrial or laboratory) conditions, can make it slightly water soluble. This makes it a little different from progesterone, which is simply and thoroughly insoluble in water, though the term “free hormone” is often applied to progesterone, as it is to thyroid. In the case of progesterone, the term “free progesterone” can be traced to experiments in which serum containing progesterone (bound to proteins) is separated by a (dialysis) membrane from a solution of similar proteins which contain no progesterone. Progesterone “dissolves in” the substance of the membrane, and the serum proteins, which also tend to associate with the membrane, are so large that they don't pass through it. On the other side, proteins coming in contact with the membrane pick up some progesterone. The progesterone that passes through is called “free progesterone,” but from that experiment, which gives no information on the nature of the interactions between progesterone and the dialysis membrane, or about its interactions with the proteins, or the proteins' interactions with the membrane, nothing is revealed about the reasons for the transmission or exchange of a certain amount of progesterone. Nevertheless, that type of experiment is used to interpret what happens in the body, where there is nothing that corresponds to the experimental set-up, except that some progesterone is associated with some protein.

有时还会使用RT3U测试,即T3树脂摄取测试,以及甲状腺素的测量。在血清样品中加入一定量的放射性T3,然后将吸附剂材料暴露于血清和放射性T3的混合物中。粘附在树脂上的辐射量称为T3吸收。实验报告给出了一个名为T7的数字,即游离甲状腺素指数。越仔细地检查这个程序,它看起来就越愚蠢,而且它看起来相当愚蠢。粘在树脂上的放射性T3会与“游离甲状腺素”相对应,这个想法本身就很奇怪,但真正有趣的问题是,“游离甲状腺素”是什么意思?甲状腺素是一种相当疏水性(不溶于水)的物质,会与血液中的蛋白质、细胞和脂蛋白结合,而不是溶于水。尽管默克指数将其描述为“不溶于水”,但它确实含有一些极性基团,在适当的(工业或实验室)条件下,可以使其略有水溶性。这使得它与黄体酮有一点不同,黄体酮是简单且完全不溶于水的,尽管“游离激素”一词通常用于黄体酮,就像它用于甲状腺一样。在黄体酮的例子中,“游离黄体酮”一词可以追溯到含有黄体酮(与蛋白质结合)的血清被透析膜从不含黄体酮的类似蛋白质溶液中分离出来的实验。黄体酮“溶解在”细胞膜的物质中,血清蛋白也倾向于与细胞膜结合,它们太大了,无法通过细胞膜。另一方面,与细胞膜接触的蛋白质吸收了一些孕酮。通过的孕酮被称为“游离孕酮”但从那个实验中,没有给出孕酮和透析膜之间相互作用的性质的信息,也没有给出它与蛋白质的相互作用,或者蛋白质与透析膜的相互作用的信息,关于一定数量的孕酮传递或交换的原因,没有透露任何信息。然而,这种类型的实验是用来解释体内发生了什么,除了一些黄体酮与一些蛋白质有关之外,没有任何与实验设置相对应的东西。

The idea that the “free hormone” is the active form has been tested in a few situations, and in the case of the thyroid hormone, it is clearly not true for the brain, and some other organs. The protein-bound hormone is, in these cases, the active form; the associations between the “free hormone” and the biological processes and diseases will be completely false, if they are ignoring the active forms of the hormone in favor of the less active forms. The conclusions will be false, as they are when T4 is measured, and T3 ignored. Thyroid-dependent processes will appear to be independent of the level of thyroid hormone; hypothyroidism could be caller hyperthyroidism.

“游离激素”是活性形式的观点已经在一些情况下进行了测试,在甲状腺激素的例子中,这显然对大脑和其他器官是不正确的。在这些情况下,蛋白质结合激素是活性形式;“游离激素”与生物过程和疾病之间的联系将是完全错误的,如果他们忽视了激素的活性形式而倾向于不那么活跃的形式。结论将是错误的,因为他们是测量T4,而忽略T3。甲状腺依赖性过程似乎与甲状腺激素水平无关;甲状腺功能减退可能是甲状腺机能亢进。

Although progesterone is more fat soluble than cortisol and the thyroid hormones, the behavior of progesterone in the blood illustrates some of the problems that have to be considered for interpreting thyroid physiology. When red cells are broken up, they are found to contain progesterone at about twice the concentration of the serum. In the serum, 40 to 80% of the progesterone is probably carried on albumin. (Albumin easily delivers its progesterone load into tissues.) Progesterone, like cholesterol, can be carried on/in the lipoproteins, in moderate quantities. This leaves a very small fraction to be bound to the “steroid binding globulin.” Anyone who has tried to dissolve progesterone in various solvents and mixtures knows that it takes just a tiny amount of water in a solvent to make progesterone precipitate from solution as crystals; its solubility in water is essentially zero. “Free” progesterone would seem to mean progesterone not attached to proteins or dissolved in red blood cells or lipoproteins, and this would be zero. The tests that purport to measure free progesterone are measuring something, but not the progesterone in the watery fraction of the serum.

尽管黄体酮比皮质醇和甲状腺激素更易于脂溶,但黄体酮在血液中的行为说明了解释甲状腺生理学时必须考虑的一些问题。当红细胞被分解时,发现它们含有大约两倍于血清浓度的黄体酮。在血清中,40 - 80%的孕酮可能通过白蛋白携带。(白蛋白很容易将黄体酮输送到组织中。)黄体酮和胆固醇一样,可以适量地存在于脂蛋白中。这就留下了非常小的一部分与“类固醇结合球蛋白”结合。任何尝试过在各种溶剂和混合物中溶解黄体酮的人都知道,只要在溶剂中加入少量的水,黄体酮就会从溶液中沉淀成晶体;它在水中的溶解度基本上为零。“游离”孕酮似乎意味着孕酮不附着在蛋白质上或溶解在红细胞或脂蛋白中,这将是零。那些声称能测量游离孕酮的测试确实测量了一些东西,但并没有测量血清中水分部分的孕酮。

The thyroid hormones associate with three types of simple proteins in the serum: Transthyretin (prealbumin), thyroid binding globulin, and albumin. A very significant amount is also associated with various serum lipoproteins, including HDL, LDL, and VLDL (very low density lipoproteins). A very large portion of the thyroid in the blood is associated with the red blood cells. When red cells were incubated in a medium containing serum albumin, with the cells at roughly the concentration found in the blood, they retained T3 at a concentration 13.5 times higher than that of the medium. In a larger amount of medium, their concentration of T3 was 50 times higher than the medium's. When laboratories measure the hormones in the serum only, they have already thrown out about 95% of the thyroid hormone that the blood contained.

甲状腺激素与血清中三种简单蛋白有关:转甲状腺素(前白蛋白)、甲状腺结合球蛋白和白蛋白。一个非常重要的量也与各种血清脂蛋白有关,包括HDL、LDL和VLDL(极低密度脂蛋白)。血液中很大一部分甲状腺与红血球有关。当红细胞在含有血清白蛋白的培养基中孵育时,细胞浓度与血液中发现的浓度大致相同,它们保留的T3浓度比培养基的浓度高13.5倍。在较大量的培养基中,其T3浓度是培养基的50倍。当实验室只测量血清中的激素时,他们已经排除了血液中95%的甲状腺激素。

The T3 was found to be strongly associated with the cells' cytoplasmic proteins, but to move rapidly between the proteins inside the cells and other proteins outside the cells.

T3被发现与细胞的细胞质蛋白紧密相关,但在细胞内的蛋白质和细胞外的其他蛋白质之间快速移动。

When people speak of hormones travelling “on” the red blood cells, rather than “in” them, it is a concession to the doctrine of the impenetrable membrane barrier.

当人们说激素“在”红细胞上流动而不是“在”红细胞里流动时,这是对无法穿透的膜屏障学说的让步。

Much more T3 bound to albumin is taken up by the liver than the small amount identified in vitro as free T3 (Terasaki, et al., 1987). The specific binding of T3 to albumin alters the protein's electrical properties, changing the way the albumin interacts with cells and other proteins. (Albumin becomes electrically more positive when it binds the hormone; this would make the albumin enter cells more easily. Giving up its T3 to the cell, it would become more negative, making it tend to leave the cell.) This active role of albumin in helping cells take up T3 might account for its increased uptake by the red cells when there were fewer cells in proportion to the albumin medium. This could also account for the favorable prognosis associated with higher levels of serum albumin in various sicknesses.

肝脏吸收更多与白蛋白结合的T3,远多于体外鉴定的游离T3 (Terasaki等,1987)。T3与白蛋白的特异性结合改变了蛋白质的电学性质,改变了白蛋白与细胞和其他蛋白质相互作用的方式。(白蛋白在与激素结合时电性更强;这将使白蛋白更容易进入细胞。把它的T3给细胞,它会变得更负,使它倾向于离开细胞。)白蛋白在帮助细胞摄取T3方面的这种积极作用,可能是由于当白蛋白培养基中细胞数量相对较少时,红细胞对T3的摄取增加的原因。这也解释了不同疾病中血清白蛋白水平较高的预后良好的原因。

When T3 is attached chemically (covalently, permanently) to the outside of red blood cells, apparently preventing its entry into other cells, the presence of these red cells produces reactions in other cells that are the same as some of those produced by the supposedly “free hormone.” If T3 attached to whole cells can exert its hormonal action, why should we think of the hormone bound to proteins as being unable to affect cells? The idea of measuring the “free hormone” is that it supposedly represents the biologically active hormone, but in fact it is easier to measure the biological effects than it is to measure this hypothetical entity. Who cares how many angels might be dancing on the head of a pin, if the pin is effective in keeping your shirt closed?

当T3以化学方式(共价,永久地)附着在红细胞外部,明显地阻止它进入其他细胞时,这些红细胞的存在在其他细胞中产生的反应与所谓的“自由激素”产生的反应相同。如果T3附着在整个细胞上可以发挥其激素作用,为什么我们要认为与蛋白质结合的激素不能影响细胞呢?测量“自由荷尔蒙”的想法是,它被认为代表了具有生物活性的荷尔蒙,但事实上,测量生物效应比测量这个假设的实体更容易。如果别针能有效地把你的衬衫拉紧,谁会在乎有多少天使在别针头上跳舞呢?

IV. Events in the tissues

组织中的事件

Besides the effects of commercial deception, confusion about thyroid has resulted from some biological clichés. The idea of a “barrier membrane” around cells is an assumption that has affected most people studying cell physiology, and its effects can be seen in nearly all of the thousands of publications on the functions of thyroid hormones. According to this idea, people have described a cell as resembling a droplet of a watery solution, enclosed in an oily bag which separates the internal solution from the external watery solution. The cliché is sustained only by neglecting the fact that proteins have a great affinity for fats, and fats for proteins; even soluble proteins, such as serum albumin, often have interiors that are extremely fat-loving. Since the structural proteins that make up the framework of a cell aren't “dissolved in water” (they used to be called “the insoluble proteins”), the lipophilic phase isn't limited to an ultramicroscopically thin surface, but actually constitutes the bulk of the cell.

除了商业欺骗的影响,有关甲状腺的困惑还来自于一些生物clichés。细胞周围有“屏障膜”的想法是一个假设,影响了大多数研究细胞生理学的人,它的影响可以在几乎所有关于甲状腺激素功能的出版物中看到。根据这一观点,人们把细胞描述成一个水滴状的水溶液,包裹在一个油袋里,将内部溶液和外部溶液分离。cliché之所以能维持下去,只是因为忽略了这样一个事实:蛋白质对脂肪有很大的亲和力,脂肪对蛋白质也有很大的亲和力;即使是可溶性蛋白质,如血清白蛋白,其内部也往往是非常喜欢脂肪的。由于构成细胞框架的结构蛋白并不“溶解在水中”(它们过去被称为“不溶蛋白”),亲脂相并不局限于极薄的表面,而是实际上构成了细胞的大部分。

Molecular geneticists like to trace their science from a 1944 experiment that was done by Avery., et al. Avery's group knew about an earlier experiment, that had demonstrated that when dead bacteria were added to living bacteria, the traits of the dead bacteria appeared in the living bacteria. Avery's group extracted DNA from the dead bacteria, and showed that adding it to living bacteria transferred the traits of the dead organisms to the living.

分子遗传学家喜欢从1944年艾弗里做的实验中追溯他们的科学。,等。艾弗里的团队知道一个更早的实验,这个实验证明,当死细菌被添加到活细菌中,死细菌的特征会在活细菌中出现。艾弗里的团队从死亡细菌中提取了DNA,并证明将其添加到活着的细菌中可以将死亡生物的特征转移到活着的细菌中。

In the 1930s and 1940s, the movement of huge molecules such as proteins and nucleic acids into cells and out of cells wasn't a big deal; people observed it happening, and wrote about it. But in the 1940s the idea of the barrier membrane began gaining strength, and by the 1960s nothing was able to get into cells without authorization. At present, I doubt that any molecular geneticist would dream of doing a gene transplant without a “vector” to carry it across the membrane barrier.

在20世纪30年代和40年代,蛋白质和核酸等大分子进出细胞并不是什么大事;人们观察到它的发生,并把它写下来。但在20世纪40年代,屏障膜的想法开始得到加强,到20世纪60年代,没有任何东西能够未经授权进入细胞。目前,我怀疑任何分子遗传学家都不会梦想在没有“载体”的情况下进行基因移植。

Since big molecules are supposed to be excluded from cells, it's only the “free hormone” which can find its specific port of entry into the cell, where another cliché says it must travel into the nucleus, to react with a specific site to activate the specific genes through which its effects will be expressed.

因为大型分子应该被排除在细胞,只有“自由激素”,可以找到进入细胞的特定端口,另一个陈词滥调说它必须进入细胞核,与一个特定的网站反应激活特定基因通过它将表达的影响。

I don't know of any hormone that acts that way. Thyroid, progesterone, and estrogen have many immediate effects that change the cell's functions long before genes could be activated.

我不知道有什么激素会这样。甲状腺、黄体酮和雌激素在基因被激活之前就有许多直接影响细胞功能的作用。

Transthyretin, carrying the thyroid hormone, enters the cell's mitochondria and nucleus (Azimova, et al., 1984, 1985). In the nucleus, it immediately causes generalized changes in the structure of chromosomes, as if preparing the cell for major adaptive changes. Respiratory activation is immediate in the mitochondria, but as respiration is stimulated, everything in the cell responds, including the genes that support respiratory metabolism. When the membrane people have to talk about the entry of large molecules into cells, they use terms such as “endocytosis” and “translocases,” that incorporate the assumption of the barrier. But people who actually investigate the problem generally find that “diffusion,” “codiffusion,” and absorption describe the situation adequately (e.g., B.A. Luxon, 1997; McLeese and Eales, 1996). “Active transport” and “membrane pumps” are ideas that seem necessary to people who haven't studied the complex forces that operate at phase boundaries, such as the boundary between a cell and its environment.

携带甲状腺激素的转甲状腺素进入细胞的线粒体和细胞核(Azimova等,1984,1985)。在细胞核中,它立即引起染色体结构的普遍变化,仿佛使细胞为主要的适应性变化做好准备。线粒体内的呼吸活动是即时的,但当呼吸受到刺激时,细胞内的一切都有反应,包括支持呼吸代谢的基因。当人们谈到细胞膜时,他们使用诸如“内吞作用”和“转位酶”这样的术语,这些术语包含了屏障的假设。但是,真正调查这个问题的人通常会发现,“扩散”、“共扩散”和“吸收”充分地描述了这种情况(例如,B.A. Luxon, 1997;McLeese and Eales, 1996)。“主动运输”和“膜泵”对那些还没有研究过在相边界(比如细胞与其环境之间的边界)作用的复杂力的人来说似乎是必要的想法。

V. Therapy

治疗

Years ago it was reported that Armour thyroid, U.S.P., released T3 and T4, when digested, in a ratio of 1:3, and that people who used it had much higher ratios of T3 to T4 in their serum, than people who took only thyroxine. The argument was made that thyroxine was superior to thyroid U.S.P., without explaining the significance of the fact that healthy people who weren't taking any thyroid supplement had higher T3:T4 ratios than the people who took thyroxine, or that our own thyroid gland releases a high ratio of T3 to T4. The fact that the T3 is being used faster than T4, removing it from the blood more quickly than it enters from the thyroid gland itself, hasn't been discussed in the journals, possibly because it would support the view that a natural glandular balance was more appropriate to supplement than pure thyroxine.

多年前有报道称,甲状甲状腺素(Armour thyroid, U.S.P)在消化时释放的T3和T4的比例为1:3,而且使用甲状甲状腺素的人血清中T3和T4的比例比只服用甲状腺素的人高得多。甲状腺素的论点是优于甲状腺usp,没有解释的重要性,健康的人不采取任何甲状腺补充剂有更高的T3: T4比服用甲状腺素的人,或者我们自己的甲状腺释放T3, T4的比例很高。T3的速度比使用T4,删除它从血液比它更快进入甲状腺本身,没有讨论的期刊,可能是因为它将支持的观点自然腺平衡比纯粹的甲状腺素更适当的补充。

The serum's high ratio of T4 to T3 is a pitifully poor argument to justify the use of thyroxine instead of a product that resembles the proportion of these substances secreted by a healthy thyroid gland, or maintained inside cells. About 30 years ago, when many people still thought of thyroxine as “the thryoid hormone,” someone was making the argument that “the thyroid hormone” must work exclusively as an activator of genes, since most of the organ slices he tested didn't increase their oxygen consumption when it was added. In fact, the addition of thyroxine to brain slices suppressed their respiration by 6% during the experiment. Since most T3 is produced from T4 in the liver, not in the brain, I think that experiment had great significance, despite the ignorant interpretation of the author. An excess of thyroxine, in a tissue that doesn't convert it rapidly to T3, has an antithyroid action. (See Goumaz, et al, 1987.) This happens in many women who are given thyroxine; as their dose is increased, their symptoms get worse.

血清中T4和T3的高比值是一个可怜的可怜的理由,证明使用甲状腺素而不是类似于健康甲状腺分泌或细胞内维持的这些物质的比例的产品。大约30年前,当许多人还认为甲状腺素是“甲状腺激素”时,有人提出“甲状腺激素”只能作为基因的激活剂,因为他测试的大多数器官切片在添加时并没有增加它们的耗氧量。事实上,在实验中,大脑切片中加入甲状腺素抑制了他们6%的呼吸。由于大多数T3是由肝脏中的T4产生的,而不是在大脑中产生的,所以我认为这个实验很有意义,尽管作者的解释有些无知。如果组织中的甲状腺素不能迅速转化为T3,那么过量的甲状腺素就具有抗甲状腺作用。(参见Goumaz等人,1987年)。这发生在许多服用甲状腺素的妇女身上;随着剂量的增加,他们的症状变得更糟。

The brain concentrates T3 from the serum, and may have a concentration 6 times higher than the serum (Goumaz, et al., 1987), and it can achieve a higher concentration of T3 than T4. It takes up and concentrates T3, while tending to expel T4. Reverse T3 (rT3) doesn't have much ability to enter the brain, but increased T4 can cause it to be produced in the brain. These observations suggest to me that the blood's T3:T4 ratio would be very “brain favorable” if it approached more closely to the ratio formed in the thyroid gland, and secreted into the blood. Although most synthetic combination thyroid products now use a ratio of four T4 to one T3, many people feel that their memory and thinking are clearer when they take a ratio of about three to one. More active metabolism probably keeps the blood ratio of T3 to T4 relatively high, with the liver consuming T4 at about the same rate that T3 is used.

大脑从血清中浓缩T3,其浓度可能是血清的6倍(Goumaz, et al., 1987),可以达到T3高于T4的浓度。对T3的吸收集中,对T4的排出有一定的趋势。逆行T3 (rT3)进入大脑的能力不大,但T4增加可导致大脑产生逆行T3。这些观察告诉我,如果血液中的T3:T4比例更接近甲状腺中形成的比例,并分泌到血液中,那么它将是非常“有利于大脑”的。虽然现在大多数合成组合甲状腺产品使用的是T4和T3的比例是4比1,但很多人觉得在3比1左右的比例下,记忆力和思维更加清晰。更活跃的代谢可能使血液中T3 / T4的比值保持较高,肝脏消耗T4的速率与消耗T3的速率大致相同。

Since T3 has a short half life, it should be taken frequently. If the liver isn't producing a noticeable amount of T3, it is usually helpful to take a few micorgrams per hour. Since it restores respiration and metabolic efficiency very quickly, it isn't usually necessary to take it every hour or two, but until normal temperature and pulse have been achieved and stabilized, sometimes it's necessary to take it four or more times during the day. T4 acts by being changed to T3, so it tends to accumulate in the body, and on a given dose, usually reaches a steady concentration after about two weeks.

由于T3半衰期短,应经常服用。如果肝脏不能产生明显数量的T3,每小时服用几微克通常是有帮助的。由于它能很快恢复呼吸和代谢效率,通常不需要每一两个小时服用一次,但在体温和脉搏正常并稳定下来之前,有时一天服用四次或更多是必要的。T4通过转变为T3发挥作用,所以它倾向于在体内积累,在给定的剂量下,通常在大约两周后达到稳定的浓度。

An effective way to use supplements is to take a combination T4-T3 dose, e.g., 40 mcg of T4 and 10 mcg of T3 once a day, and to use a few mcg of T3 at other times in the day. Keeping a 14-day chart of pulse rate and temperature allows you to see whether the dose is producing the desired response. If the figures aren't increasing at all after a few days, the dose can be increased, until a gradual daily increment can be seen, moving toward the goal at the rate of about 1/14 per day.

使用补充剂的一个有效方法是服用T4-T3组合剂量,例如,T4 40 mcg和T3 10 mcg,每天一次,在一天的其他时间使用少量T3。保持一个14天的脉搏率和体温图表可以让你看到剂量是否产生预期的反应。如果几天后数字没有增加,就可以增加剂量,直到每天逐渐增加,朝着每天约1/14的目标移动。

VI. Diagnosis

诊断

In the absence of commercial techniques that reflect thyroid physiology realistically, there is no valid alternative to diagnosis based on the known physiological indicators of hypothyroidism and hyperthyroidism. The failure to treat sick people because of one or another blood test that indicates “normal thyroid function,” or the destruction of patients' healthy thyroid glands because one of the tests indicates hyperthyroidism, isn't acceptable just because it's the professional standard, and is enforced by benighted state licensing boards.

在缺乏能真实反映甲状腺生理的商业技术的情况下,根据已知的甲状腺功能减退和甲状腺功能亢进的生理指标,没有有效的替代诊断方法。未能把生病的人因为一个或另一个血液测试表明甲状腺功能正常,或破坏病人的健康甲状腺因为测试表明甲状腺机能亢进,不是可接受的仅仅因为它是专业标准,并执行由愚昧的国家授权董事会。

Toward the end of the twentieth century, there has been considerable discussion of “evidence-based medicine.” Good judgment requires good information, but there are forces that would over-rule individual judgment as to whether published information is applicable to certain patients. In an atmosphere that sanctions prescribing estrogen or insulin without evidence of an estrogen deficiency or insulin deficiency, but that penalizes practitioners who prescribe thyroid to correct symptoms, the published “evidence” is necessarily heavily biased. In this context, “meta-analysis” becomes a tool of authoritarianism, replacing the use of judgment with the improper use of statistical analysis.

在20世纪末,有相当多的关于“循证医学”的讨论。良好的判断需要良好的信息,但在公布的信息是否适用于某些患者的问题上,有一些力量会推翻个人判断。在没有雌激素或胰岛素缺乏症证据的情况下开具雌激素或胰岛素处方,却惩罚开具甲状腺处方以纠正症状的医生的情况下,公开的“证据”必然存在严重的偏见。在这种背景下,“元分析”成为一种威权主义的工具,用统计分析的不当使用取代了判断的使用。

Unless someone can demonstrate the scientific invalidity of the methods used to diagnose hypothyroidism up to 1945, then they constitute the best present evidence for evaluating hypothyroidism, because all of the blood tests that have been used since 1950 have been.shown to be, at best, very crude and conceptually inappropriate methods.

除非有人能证明1945年以前用于诊断甲状腺机能减退的方法在科学上是无效的,否则它们就构成了评估甲状腺机能减退的最佳证据,因为自1950年以来使用的所有血液测试都是如此。充其量是非常粗糙和概念上不合适的方法。

Thomas H. McGavack's 1951 book, The Thyroid, was representative of the earlier approach to the study of thyroid physiology. Familiarity with the different effects of abnormal thyroid function under different conditions, at different ages, and the effects of gender, were standard parts of medical education that had disappeared by the end of the century. Arthritis, irregularities of growth, wasting, obesity, a variety of abnormalities of the hair and skin, carotenemia, amenorrhea, tendency to miscarry, infertility in males and females, insomnia or somnolence, emphysema, various heart diseases, psychosis, dementia, poor memory, anxiety, cold extremities, anemia, and many other problems were known reasons to suspect hypothyroidism. If the physician didn't have a device for measuring oxygen consumption, estimated calorie intake could provide supporting evidence. The Achilles' tendon reflex was another simple objective measurement with a very strong correlation to the basal metabolic rate. Skin electrical resistance, or whole body impedance wasn't widely accepted, though it had considerable scientific validity.

托马斯·h·麦加瓦克(Thomas H. McGavack) 1951年出版的《甲状腺》(The Thyroid)是早期甲状腺生理学研究方法的代表。了解甲状腺功能异常在不同条件、不同年龄、性别等方面的不同影响是医学教育的标准内容,到本世纪末已经消失。关节炎、生长异常、消瘦、肥胖、各种发、皮肤异常、胡萝卜素血症、闭经、流产倾向、男女不育症、失眠或嗜睡、肺气肿、各种心脏病、精神病、痴呆、记忆力差、焦虑、四肢冷、贫血、还有许多其他问题被认为是怀疑甲状腺功能减退的原因。如果医生没有测量耗氧量的设备,估计卡路里摄入量可以提供支持证据。跟腱反射是另一个简单的客观测量,与基础代谢率有很强的相关性。皮肤电阻或全身阻抗并没有被广泛接受,尽管它有相当的科学依据。

A therapeutic trial was the final test of the validity of the diagnosis: If the patient's symptoms disappeared as his temperature and pulse rate and food intake were normalized, the diagnostic hypothesis was confirmed. It was common to begin therapy with one or two grains of thyroid, and to adjust the dose according to the patient's response. Whatever objective indicator was used, whether it was basal metabolic rate, or serum cholesterol. or core temperature, or reflex relaxation rate, a simple chart would graphically indicate the rate of recovery toward normal health.

治疗性试验是诊断有效性的最终检验:如果患者的症状随着体温、脉搏频率和食物摄入量的正常化而消失,则诊断假设得到证实。通常在治疗开始时服用一到两粒甲状腺素,然后根据病人的反应调整剂量。无论使用何种客观指标,无论是基础代谢率还是血清胆固醇。或者是核心温度,或者是反射松弛率,一个简单的图表会生动地显示恢复到正常健康的速度。

REFERENCES

引用

McGavack, Thomas Hodge.: The thyroid,: St. Louis, Mosby, 1951. 646 p. ill.Several chapters contributed by various authors.Call Numbers WK200 M145t 1951 (Rare Book).

McGavack托马斯·霍奇。:甲状腺,莫斯比,圣路易斯,1951年。646 p .几章由不同的作者贡献。

Endocrinology 1979 Sep; 105(3): 605-12. Carrier-mediated transport of thyroid hormones through the rat blood-brain barrier: primary role of albumin-bound hormone. Pardridge WM.

内分泌学1979年9月;105(3): 605 - 12所示。载体介导的甲状腺激素通过大鼠血脑屏障的运输:白蛋白结合激素的主要作用。Pardridge WM。

Endocrinology 1987 Apr;120(4):1590-6. Brain cortex reverse triiodothyronine (rT3) and triiodothyronine concentrations under steady state infusions of thyroxine and rT3. Goumaz MO, Kaiser CA, Burger A.G.

内分泌学1987年4月,120(4):1590 - 6。在稳定输注甲状腺素和rT3时,大脑皮层逆转三碘甲状腺原氨酸(rT3)和三碘甲状腺原氨酸的浓度。Goumaz MO, Kaiser CA, Burger A.G.

J Clin Invest 1984 Sep;74(3):745-52. Tracer kinetic model of blood-brain barrier transport of plasma protein-bound ligands. Empiric testing of the free hormone hypothesis. Pardridge WM, Landaw EM. Previous studies have shown that the fraction of hormone or drug that is plasma protein bound is readily available for transport through the brain endothelial wall, i.e., the blood-brain barrier (BBB). To test whether these observations are reconcilable with the free-hormone hypothesis, a tracer-kinetic model is used Endocrinology 113(1), 391-8, 1983, Stimulation of sugar transport in cultured heart cells by triiodothyronine (T2) covalently bound to red blood cells and by T3 in the presence of serum, Dickstein Y, Schwartz H, Gross J, Gordon A.

J Clin Invest 1984 9月;74(3):745-52。血浆蛋白结合配体血脑屏障运输的示踪动力学模型。自由荷尔蒙假说的实证检验。此前的研究表明,血浆蛋白结合的激素或药物组分很容易通过脑内皮壁,即血脑屏障(BBB)运输。来测试这些观察是否可调和的free-hormone假说,tracer-kinetic模型使用内分泌学113(1),391 - 8,1983年,刺激培养的心脏细胞的糖运输三碘甲状腺氨酸(T2)共价结合红细胞和血清T3面前

Endocrinology 1987 Sep; 121(3): 1185-91. Stereospecificity of triiodothyronine transport into brain, liver, and salivary gland: role of carrier- and plasma protein-mediated transport. Terasaki T, Pardridge WM. J. Neurophysiol 1994 Jul;72(1):380-91. Film autoradiography identifies unique features of [125I]3,3'5'-(reverse) triiodothyronine transport from blood to brain. Cheng LY, Outterbridge LV, Covatta ND, Martens DA, Gordon JT, Dratman MB

内分泌学1987年9月;121(3): 1185 - 91。三碘甲状腺原氨酸转运到脑、肝和唾液腺的立体特异性:载体和血浆蛋白介导的转运的作用。Terasaki T, Pardridge WM。中国神经生理学杂志1994年7月;72(1):380-91。电影自放射成像确定了[125I]3,3'5'-(反向)三碘甲状腺原氨酸从血液到大脑运输的独特特征。Cheng LY, Outterbridge LV, Covatta ND, Martens DA, Gordon JT, Dratman MB

Brain Res 1991 Jul 19;554(1-2):229-36. Transport of iodothyronines from bloodstream to brain: contributions by blood:brain and choroid plexus:cerebrospinal fluid barriers. Dratman MB, Crutchfield FL, Schoenhoff MB..

脑研究1991 7月19日;554(1-2):229-36。碘甲状腺素从血流到大脑的运输:通过血液:大脑和脉络膜丛:脑脊液屏障的贡献。Dratman MB, Crutchfield FL, Schoenhoff MB..

Mech Ageing Dev 1990 Mar 15;52(2-3):141-7. Blood-brain transport of triiodothyronine is reduced in aged rats. Mooradian AD Geriatrics Section, Tucson VA Medical Center, AZ.

机械老化发展1990 3月15日;52(2-3):141-7。老年大鼠三碘甲状腺原氨酸的血脑运输减少。亚利桑那州图森VA医疗中心Mooradian老年痴呆科

Endocrinology 1987 Sep;121(3):1185-91. Stereospecificity of triiodothyronine transport into brain, liver, and salivary gland: role of carrier- and plasma protein-mediated transport. Terasaki T, Pardridge WM. J Clin Invest 1984 Sep;74(3):745-52. Tracer kinetic model of blood-brain barrier transport of plasma protein-bound ligands. Empiric testing of the free hormone hypothesis. Pardridge WM, Landaw EM.

内分泌学1987年9月,121(3):1185 - 91。三碘甲状腺原氨酸转运到脑、肝和唾液腺的立体特异性:载体和血浆蛋白介导的转运的作用。Terasaki T, Pardridge WM。J Clin Invest 1984 9月;74(3):745-52。血浆蛋白结合配体血脑屏障运输的示踪动力学模型。自由荷尔蒙假说的实证检验。Pardridge WM, Landaw EM。

Endocrinology 1980 Dec;107(6):1705-10. Transport of thyroid and steroid hormones through the blood-brain barrier of the newborn rabbit: primary role of protein-bound hormone. Pardridge WM, Mietus LJ. Endocrinology 1979 Sep; 105(3): 605-12. Carrier-mediated transport of thyroid hormones through the rat blood-brain barrier: primary role of albumin-bound hormone. Pardridge WM.

内分泌学1980年12月,107(6):1705 - 10。甲状腺和类固醇激素通过新生兔血脑屏障的运输:蛋白结合激素的主要作用。Pardridge WM, miietus LJ。内分泌学1979年9月;105(3): 605 - 12所示。载体介导的甲状腺激素通过大鼠血脑屏障的运输:白蛋白结合激素的主要作用。Pardridge WM。

Endocrinology 1975 Jun;96(6):1357-65. Triiodothyronine binding in rat anterior pituitary, posterior pituitary, median eminence and brain. Gordon A, Spira O.

内分泌学1975年6月,96(6):1357 - 65。三碘甲状腺原氨酸结合于大鼠垂体前叶、垂体后叶、正中隆起及脑。Gordon A, Spira O。

Endocr Rev 1989 Aug;10(3):232-74. The free hormone hypothesis: a physiologically based mathematical model. Mendel CM. Biochim Biophys Acta 1991 Mar 4;1073(2):275-84. Transport of steroid hormones facilitated by serum proteins. Watanabe S, Tani T, Watanabe S, Seno M Kanagawa.

endr 1989 8月;10(3):232-74。自由荷尔蒙假说:一种基于生理学的数学模型。孟德尔厘米。Acta bioologica sinica 1991 3月4日;1073(2):275-84。血清蛋白促进类固醇激素的转运。

D Novitzky, H Fontanet, M Snyder, N Coblio, D Smith, V Parsonnet, Impact of triiodothyronine on the survival of high-risk patients undergoing open heart surgery, Cardiology, 1996, Vol 87, Iss 6, pp 509-515. Biochim Biophys Acta 1997. Jan 16;1318(1-2):173-83 Regulation of the energy coupling in mitochondria by some steroid and thyroid hormones. Starkov AA, Simonyan RA, Dedukhova VI, Mansurova SE, Palamarchuk LA, Skulachev VP

D Novitzky, H Fontanet, M Snyder, N Coblio, D Smith, V Parsonnet,三碘甲状腺原氨酸对接受心内直视手术高危患者生存的影响,心脏病学,1996,Vol 87, Iss 6, pp 509-515。生物化学学报1997。1318(1-2):173-83某些类固醇和甲状腺激素对线粒体能量耦合的调控。Starkov AA, Simonyan RA, Dedukhova VI, Mansurova SE, Palamarchuk LA, Skulachev

Thyroid 1996 Oct;6(5):531-6. Novel actions of thyroid hormone: the role of triiodothyronine in cardiac transplantation. Novitzky D. Rev Med Chil 1996 Oct;124(10):1248-50. [Severe cardiac failure as complication of primary hypothyroidism]. Novik V, Cardenas IE, Gonzalez R, Pena M, Lopez Moreno JM.

甲状腺10月1996;6(5):531 - 6。甲状腺激素的新作用:三碘甲状腺原氨酸在心脏移植中的作用。诺维茨基医学期刊1996年10月;124(10):1248-50。[原发性甲状腺功能减退合并严重心力衰竭]。Novik V, Cardenas IE, Gonzalez R, Pena M, Lopez Moreno JM

Cardiology 1996 Nov-Dec;87(6):509-15. Impact of triiodothyronine on the survival of high-risk patients undergoing open heart surgery. Novitzky D, Fontanet H, Snyder M, Coblio N, Smith D, Parsonnet V Curr Opin Cardiol 1996 Nov;11(6):603-9. The use of thyroid hormone in cardiac surgery. Dyke C

心脏病学1996年11 - 12月,87(6):509 - 15所示。三碘甲状腺原氨酸对心脏直视手术高危患者生存的影响。Novitzky D, Fontanet H, Snyder M, Coblio N, Smith D, Parsonnet V Curr Opin Cardiol 1996 Nov;11(6):603-9。甲状腺激素在心脏手术中的应用。

N Koibuchi, S Matsuzaki, K Ichimura, H Ohtake, S Yamaoka. Ontogenic changes in the expression of cytochrome c oxidase subunit I gene in the cerebellar cortex of the perinatal hypothyroid rat. Endocrinology, 1996, Vol 137, Iss 11, pp 5096-5108.

N Koibuchi, S Matsuzaki, K Ichimura, H Ohtake, S Yamaoka。围生期甲状腺机能减退大鼠小脑皮质细胞色素c氧化酶亚基I基因表达的个体发生变化。内分泌学,1996,第137卷,第11期,第5096-5108页。

Biokhimiia 1984 Aug;49(8):1350-6. [The nature of thyroid hormone receptors. Translocation of thyroid hormones through plasma membranes]. [Article in Russian] Azimova ShS, Umarova GD, Petrova OS, Tukhtaev KR, Abdukarimov A. The in vivo translocation of thyroxine-binding blood serum prealbumin (TBPA) was studied. It was found that the TBPA-hormone complex penetrates-through the plasma membrane into the cytoplasm of target cells. Electron microscopic autoradiography revealed that blood serum TBPA is localized in ribosomes of target cells as well as in mitochondria, lipid droplets and Golgi complex. Negligible amounts of the translocated TBPA is localized in lysosomes of the cells insensitive to thyroid hormones (spleen macrophages). Study of T4- and T3-binding proteins from rat liver cytoplasm demonstrated that one of them has the antigenic determinants common with those of TBPA. It was shown autoimmunoradiographically that the structure of TBPA is not altered during its translocation.

Biokhimiia 1984年8月,49(8):1350 - 6。甲状腺激素受体的性质甲状腺激素通过细胞膜的转运]。Azimova ShS, Umarova GD, Petrova OS, Tukhtaev KR, Abdukarimov A.研究了甲状腺素结合血清前白蛋白(TBPA)的体内易位。研究发现,tba -激素复合物通过质膜渗透到靶细胞的细胞质中。电镜自显影显示血清TBPA定位于靶细胞核糖体、线粒体、脂滴和高尔基复合物。可忽略数量的易位TBPA定位于对甲状腺激素不敏感的细胞(脾脏巨噬细胞)的溶酶体中。对大鼠肝细胞质中T4-和t3结合蛋白的研究表明,其中一种蛋白具有与TBPA相同的抗原决定因子。自身免疫放射学显示,TBPA的结构在其易位过程中没有改变。

Am J Physiol 1997 Sep;273(3 Pt 1):C859-67. Cytoplasmic codiffusion of fatty acids is not specific for fatty acid binding protein. Luxon BA, Milliano MT [The nature of thyroid hormone receptors. Intracellular functions of thyroxine-binding prealbumin] Azimova ShS; Normatov K; Umarova GD; Kalontarov AI; Makhmudova AA, Biokhimiia 1985 Nov;50(11):1926-32. The effect of tyroxin-binding prealbumin (TBPA) of blood serum on the template activity of chromatin was studied. It was found that the values of binding constants of TBPA for T3 and T4 are 2 X 10(-11) M and 5 X 10(-10) M, respectively. The receptors isolated from 0.4 M KCl extract of chromatin and mitochondria as well as hormone-bound TBPA cause similar effects on the template activity of chromatin. Based on experimental results and the previously published comparative data on the structure of TBPA, nuclear, cytoplasmic and mitochondrial receptors of thyroid hormones as well as on translocation across the plasma membrane and intracellular transport of TBPA, a conclusion was drawn, which suggested that TBPA is the “core” of the true thyroid hormone receptor. It was shown that T3-bound TBPA caused histone H1-dependent conformational changes in chromatin. Based on the studies with the interaction of the TBPA-T3 complex with spin-labeled chromatin, a scheme of functioning of the thyroid hormone nuclear receptor was proposed.

Am J Physiol 1997 Sep;273(3 Pt 1):C859-67。脂肪酸的胞质共扩散对脂肪酸结合蛋白没有特异性。甲状腺激素受体的性质[j]。Azimova ShS的细胞内功能Normatov K;Umarova GD;Kalontarov人工智能;马赫穆多瓦,1985年11月;50(11):1926-32。研究了血清酪氨酸结合前白蛋白(TBPA)对染色质模板活性的影响。结果表明,TBPA对T3和T4的结合常数分别为2 × 10(-11) M和5 × 10(-10) M。从0.4 M KCl提取的染色质和线粒体以及激素结合的TBPA中分离的受体对染色质的模板活性有类似的影响。根据实验结果和之前发表的甲状腺激素核、胞质、线粒体受体的结构以及TBPA跨质膜转运和细胞内转运的对比数据,得出结论:这表明TBPA是真正的甲状腺激素受体的“核心”。结果表明,t3结合的TBPA引起染色质中组蛋白h1依赖的构象变化。在研究TBPA-T3复合物与自旋标记染色质相互作用的基础上,提出了甲状腺激素核受体的功能方案。

[The nature of thyroid hormone receptors. Thyroxine- and triiodothyronine-binding proteins of mitochondria] Azimova ShS; Umarova GD; Petrova OS; Tukhtaev KR; Abdukarimov A. Biokhimiia 1984 Sep;49(9):1478-85. T4- and T3-binding proteins of rat liver were studied. It was found that the external mitochondrial membranes and matrix contain a protein whose electrophoretic mobility is similar to that of thyroxine-binding blood serum prealbumin (TBPA) and which binds either T4 or T3. This protein is precipitated by monospecific antibodies against TBPA. The internal mitochondrial membrane has two proteins able to bind thyroid hormones, one of which is localized in the cathode part of the gel and binds only T3, while the second one capable of binding T4 rather than T3 and possessing the electrophoretic mobility similar to that of TBPA.

甲状腺激素受体的性质线粒体的甲状腺素和三碘甲状腺素结合蛋白Umarova GD;佩特洛娃操作系统;Tukhtaev KR;Abdukarimov A. Biokhimiia 1984 9月;49(9):1478-85。对大鼠肝脏T4-和t3结合蛋白进行了研究。结果发现,线粒体外膜和基质中含有一种蛋白,其电泳流动性与甲状腺素结合血清前白蛋白(TBPA)相似,并与T4或T3结合。该蛋白可由抗TBPA的单特异性抗体沉淀。内部的线粒体膜两种蛋白质能够绑定甲状腺激素,其中一个是本地化的阴极凝胶和结合T3的一部分,而第二个能够绑定T3和T4而不是拥有TBPA的电泳淌度相似。

Radioimmunoprecipitation with monospecific antibodies against TBPA revealed that this protein also the antigenic determinants common with those of TBPA. The in vivo translocation of 125I-TBPA into submitochondrial fractions was studied. The analysis of densitograms of submitochondrial protein fraction showed that both TBPA and hormones are localized in the same protein fractions. Electron microscopic autoradiography demonstrated that 125I-TBPA enters the cytoplasm through the external membrane and is localized on the internal mitochondrial membrane and matrix.

用抗TBPA单特异性抗体进行放射免疫沉淀,发现该蛋白也是与TBPA共同的抗原决定因素。研究了125I-TBPA在体内向亚线粒体部分的移位。亚线粒体蛋白组分密度图分析表明,TBPA和激素均定位于同一蛋白组分。电镜自显影显示125I-TBPA通过外膜进入细胞质,定位于线粒体内膜和基质。

[The nature of thyroid hormone receptors. Translocation of thyroid hormones through plasma membranes]. Azimova ShS; Umarova GD; Petrova OS; Tukhtaev KR; Abdukarimov A. Biokhimiia 1984 Aug;49(8):1350-6.. The in vivo translocation of thyroxine- binding blood serum prealbumin (TBPA) was studied. It was found that the TBPA-hormone complex penetrates-through the plasma membrane into the cytoplasm of target cells. Electron microscopic autoradiography revealed that blood serum TBPA is localized in ribosomes of target cells as well as in mitochondria, lipid droplets and Golgi complex. Negligible amounts of the translocated TBPA is localized in lysosomes of the cells insensitive to thyroid hormones (spleen macrophages). Study of T4- and T3-binding proteins from rat liver cytoplasm demonstrated that one of them has the antigenic determinants common with those of TBPA. It was shown autoimmunoradiographically that the structure of TBPA is not altered during its translocation. Endocrinology 1987 Apr;120(4):1590-6 Brain cortex reverse triiodothyronine (rT3) and triiodothyronine concentrations under steady state infusions of thyroxine and rT3. Goumaz MO, Kaiser CA, Burger AG.

甲状腺激素受体的性质甲状腺激素通过细胞膜的转运]。Azimova啦;Umarova GD;佩特洛娃操作系统;Tukhtaev KR;Abdukarimov A. Biokhimiia 1984 8月;49(8):1350-6..研究了甲状腺素结合血清前白蛋白(TBPA)的体内易位。研究发现,tba -激素复合物通过质膜渗透到靶细胞的细胞质中。电镜自显影显示血清TBPA定位于靶细胞核糖体、线粒体、脂滴和高尔基复合物。可忽略数量的易位TBPA定位于对甲状腺激素不敏感的细胞(脾脏巨噬细胞)的溶酶体中。对大鼠肝细胞质中T4-和t3结合蛋白的研究表明,其中一种蛋白具有与TBPA相同的抗原决定因子。自身免疫放射学显示,TBPA的结构在其易位过程中没有改变。在稳定输注甲状腺素和rT3的情况下,大脑皮层逆转三碘甲状腺原氨酸(rT3)和三碘甲状腺原氨酸的浓度。Goumaz MO, Kaiser CA, Burger AG。

Gen Comp Endocrinol 1996 Aug;103(2):200-8 Characteristics of the uptake of 3,5,3'-triiodo-L-thyronine and L-thyroxine into red blood cells of rainbow trout (Oncorhynchus mykiss). McLeese JM, Eales JG.

虹鳟(Oncorhynchus mykiss)血红细胞摄取3,5,3'-三碘- l -甲状腺原氨酸和l -甲状腺素的特征。McLeese JM, Eales JG。

Prog Neuropsychopharmacol Biol Psychiatry 1998 Feb;22(2):293-310. Increase in red blood cell triiodothyronine uptake in untreated unipolar major depressed patients compared to healthy volunteers. Moreau X, Azorin JM, Maurel M, Jeanningros R.

《神经精神药理学生物精神病学》1998年2月22日第2期:293-310。与健康志愿者相比,未经治疗的单极重性抑郁症患者红细胞三碘甲状腺原氨酸摄取增加。Moreau X, Azorin JM, Maurel M, Jeanningros R。

Biochem J 1982 Oct 15;208(1):27-34. Evidence that the uptake of tri-iodo-L-thyronine by human erythrocytes is carrier-mediated but not energy-dependent. Docter R, Krenning EP, Bos G, Fekkes DF, Hennemann G. J Clin Endocrinol Metab 1990 Dec;71(6):1589-95. Transport of thyroid hormones by human erythrocytes: kinetic characterization in adults and newborns. Osty J, Valensi P, Samson M, Francon J, Blondeau JP. J Endocrinol Invest 1999 Apr;22(4):257-61. Kinetics of red blood cell T3 uptake in hypothyroidism with or without hormonal replacement, in the rat. Moreau X, Lejeune PJ, Jeanningros R.

生物化学学报1982 10月15日;208(1):27-34。证据表明人类红细胞摄取三碘- l -甲状腺原氨酸是载体介导的,而不是能量依赖的。dr . R, Krenning EP, Bos G, Fekkes DF, Hennemann G. J clinical Endocrinol Metab 1990 Dec;71(6):1589-95。人红细胞运输甲状腺激素:成人和新生儿的动力学特性。Osty J, Valensi P, Samson M, Francon J, Blondeau JP。J Endocrinol Invest 1999年4月22日:257-61。大鼠甲状腺功能减退伴或不伴激素替代的红细胞T3摄取动力学Moreau X, Lejeune PJ, Jeanningros R

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