Endocrine evaluation for muscle pain.
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Addison Disease↗
Biomedical subjects
S Benvenga
Publications and source records attributed to S Benvenga.
Usefulness of L-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial.
Old studies in animals and unblinded studies in a few hyperthyroid patients suggested that L -carnitine is a periferal antagonist of thyroid hormone action at least in some tissues. This conclusion was substantiated by our recent observation that carnitine inhibits thyroid hormone entry into the nucleus of hepatocytes, neurons, and fibroblasts. In the randomized, double-blind, placebo-controlled 6-month trial reported here, we assessed whether 2 or 4 g/d oral L-carnitine were able to both reverse and prevent/minimize nine hyperthyroidism- related symptoms. We also evaluated changes on nine thyroid hormone-sensitive biochemical parameters and on vertebral and hip mineral density (bone mineral density). Fifty women under a fixed TSH-suppressive dose of L -T(4) for all 6 months were randomly allocated to five groups of 10 subjects each. Group 0 associated placebo for 6 months; groups A2 and A4 started associating placebo (first bimester), substituted placebo with 2 or 4 g/d carnitine (second bimester), and then returned to the association with placebo. Groups B2 and B4 started associating 2 and 4 g/d carnitine for the first two bimesters, and then substituted carnitine with placebo (third bimester). Symptoms and biochemical parameters worsened in group 0. In group A, symptoms and biochemical parameters worsened during the first bimester, returned to baseline or increased minimally during the second bimester (except osteocalcin and urinary OH-proline), and worsened again in the third bimester. In group B, symptoms and biochemical parameters (except osteocalcin and urinary OH-proline) did not worsen or even improved over the first 4 months; they tended to worsen in the third bimester. In both the A and B groups, the two doses of carnitine were similarly effective. At the end of the trial, bone mineral density tended to increase in groups B and A (B > A). In conclusion, L-carnitine is effective in both reversing and preventing symptoms of hyperthyroidism and has a beneficial effect on bone mineralization. Because hyperthyroidism depletes the body deposits of carnitine and since carnitine has no toxicity, teratogenicity, contraindications and interactions with drugs, carnitine can be of clinical use.
Administration, Oral↗
Euthyroid hyperthyrotropinemia secondary to hyperestrogenemia in a male with congenital adrenal hyperplasia.
A 10-year-old boy with congenital adrenal hyperplasia and associated hyperplastic testicular adrenal rests had high serum concentrations of 17-OH progesterone (17-OHP), estradiol (E2), testosterone (T), and basal and TRH-stimulated TSH and PRL, but normal thyroid hormones (T3, T4, FT3, FT4) and thyroxine-binding globulin (TBG). Upon dexamethasone therapy, steroid hormones returned progressively toward normal as did both PRL and TSH; PRL declined faster than TSH. Serum E2 correlated better with PRL than with TSH. Therefore, the responsiveness of the thyrotrophs to the ambient concentration of E2 is lower and slower than that of the lactotrophs. In the context of the inconclusive data on the role of estrogens in controlling the secretion of TSH in humans, our case suggests that E2 does stimulate the secretion of basal and TRH-elicited both TSH and PRL, and that this positive action is unopposed by T. In contrast, T antagonizes the estrogen-induced increase in serum TBG. We also postulate that E2 might impair the bioactivity of TSH, in order to explain (i) the approximate 3-fold increase in serum TSH coexisting with a normally sized (rather than enlarged) thyroid and normal (rather than increased) serum thyroid hormones, and (ii) the inability of TRH-stimulated TSH to acutely raise FT3 serum levels.
17-alpha-Hydroxyprogesterone↗
Myxedema coma of both primary and secondary origin, with non-classic presentation and extremely elevated creatine kinase.
Myxedema coma is a rare, often fatal endocrine emergency that concerns elderly patients with long-standing primary hypothyroidism; myxedema coma of central origin is exceedingly rare. Here, we report a 37-year-old woman in whom classical symptoms of hypothyroidism had been absent. Six years earlier, she had severe obstetric hemorrhage and, shortly after, two subsequent episodes of pericardial effusion. On the day of admission, pericardiocentesis was performed for the third episode of pericardial effusion. Because of the subsequent grave arrhythmias and unconsciousness, she was transferred to our ICU. Prior to the endocrine consultation, a silent myocardial infarction had been suspected, based on the extremely high serum levels of creatine kinase (CK) and isoenzyme CK-MB. However, based on thyroid sonography, pituitary computed tomography, elevated titers of antithyroid antibodies and pituitary stimulation tests, the final diagnosis was myxedema coma of dual origin: an atrophic variant of Hashimoto's thyroiditis and post-necrotic pituitary atrophy (Sheehan syndrome). Substitutive therapy caused a prompt clinical amelioration and normalization of CK levels. Our patient is the first case of myxedema coma of double etiology, and illustrates how its presentation deviates markedly from the one endocrinologists and physicians at ICU are prepared to encounter. In addition, cardiac problems as those of our patient should not discourage from substitutive treatment (using L-thyroxine and the gastrointestinal route of absorption), if the age is relatively low.
Adult↗
Carnitine is a naturally occurring inhibitor of thyroid hormone nuclear uptake.
Carnitine (3-hydroxy-4N-trimethylammoniumbutanoate) is a naturally occurring quaternary amine that is ubiquitous in mammalian tissues (concentrations in the order of mM). Based on limited studies of approximately 40 years ago, carnitine was considered to be a peripheral antagonist of thyroid hormone (TH) action. These interesting observations have not been explored. To study the biologic basis of this effect, we tested the following possibilities in three TH-responsive cell lines: (1) inhibition of TH entry into cells; (2) inhibition of TH entry into the nucleus; (3) inhibition of TH interaction with the isolated nuclei; and (4) facilitated efflux of TH from cells. On a preliminary basis we had verified that these cell lines (human skin fibroblasts, human hepatoma cells HepG2, and mouse neuroblastoma cells NB 41A3) take up 14Ccarnitine; however, there was no 14Ccarnitine uptake into the nuclei. Concentrations of unlabeled carnitine as high as 100 mM did not affect (125I)T3 binding to isolated nuclei or exit of TH from cells, thus excluding possibilities numbered 3 and 4. At 10 mM camitine, (125I)T3 and (125I)T4 whole-cell uptake was inhibited by approximately 20% in fibroblasts and in HepG2, but by approximately 5% in NB 41A3 cells. Inhibition of T3 nuclear uptake was evaluated in HepG2 and NB 41A3 cells. At 10 mM carnitine, inhibition of T3 nuclear uptake was disproportionately higher, namely approximately 25% in neurons and 35% in hepatocytes. At 50 mM carnitine, there was a minimal additional decrease in whole-cell uptake of either hormone but a marked decrease in T3 nuclear uptake. The latter inhibition was approximately 60% in neurons and 70% in hepatocytes. We are aware of no inhibitor of TH uptake that has such a markedly different effect on the nuclear versus whole-cell uptake. Our data are consistent with carnitine being a peripheral antagonist of TH action, and they indicate a site of inhibition at or before the nuclear envelope.
Animals↗
Clinical review 113: Hypopituitarism secondary to head trauma.
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Adult↗
Altered thyroid hormone binding to plasma lipoproteins in the syndrome of resistance to thyroid hormones.
Lipoproteins, especially HDL, are carriers of a small fraction of the thyroid hormones in plasma and participate in the intracellular transport of T4. In previous work we showed that a brief period of hypothyroidism alters the hormone distribution among the lipoproteins, causing a decrease in VLDL and LDL binding despite a relative increase in VLDL and LDL cholesterol, an increase in HDL binding, and a reversal of T4 and T3 binding to the smallest HDL size subgroup. The present study of three patients with thyroid hormone resistance and largely compensated hypothyroidism showed thyroid hormone distribution that differed markedly from both normal and hypothyroid subjects. The most striking difference was a much lower binding of both T4 and T3 to HDL and a much higher binding to LDL. If confirmed in a larger group of patients, this might serve as a marker for thyroid hormone resistance.
Cholesterol↗
Lack of sexual activity from erectile dysfunction is associated with a reversible reduction in serum testosterone.
The role of androgenic hormones in human sexuality, in the mechanism of erection and in the pathogenesis of impotence is under debate. While the use of testosterone is common in the clinical therapy of male erectile dysfunction, hypogonadism is a rare cause of impotence. We evaluated serum testosterone levels in men with erectile dysfunction resulting either from organic or non-organic causes before and after non-hormonal impotence therapy. Eighty-three consecutive cases of impotence (70% organic, 30% non-organic, vascular aetiology being the most frequent) were subjected to hormonal screening before and after various psychological, medical (prostaglandin E1, yohimbine) or mechanical therapies (vascular surgery, penile prostheses, vacuum devices). Thirty age-matched healthy men served as a control group. Compared to controls, patients with impotence resulting from both organic and non-organic causes showed reduced serum levels of both total testosterone (11.1 +/- 2.4 vs. 17.7 +/- 5.5 nmol/L) and free testosterone (56.2 +/- 22.9 vs. 79.4 +/- 27.0 pmol/L) (both p < 0.001). Irrespective of the different aetiologies and of the various impotence therapies, a dramatic increase in serum total and free testosterone levels (15.6 +/- 4.2 nmol/L and 73.8 +/- 22.5 pmol/L, respectively) was observed in patients who achieved normal sexual activity 3 months after commencing therapy (p < 0.001). On the contrary, serum testosterone levels did not change in patients in whom therapies were ineffective. Since the pre-therapy low testosterone levels were independent of the aetiology of impotence, we hypothesize that this hormonal pattern is related to the loss of sexual activity, as demonstrated by its normalization with the resumption of coital activity after different therapies. The corollary is that sexual activity may feed itself throughout the increase in testosterone levels.
Adolescent↗
Loss of heterozygosity of the long arm of chromosome 7 in follicular and anaplastic thyroid cancer, but not in papillary thyroid cancer.
Papillary thyroid cancer (PTC), but neither the follicular nor the anaplastic histotype [follicular thyroid cancer (FTC), anaplastic thyroid cancer (ATC)], overexpresses simultaneously the protooncogene HGF (hepatocyte growth factor) and its receptor HGF-R (or c-met). Because 1) HGF and c-met map to chromosome 7q21 and 7q31, respectively, 2) FTC loses genetic material at multiple loci with a frequency much higher than PTC, and 3) loss of heterozygosity (LOH) on 7q has been previously found in various tumors, we tested the hypothesis that both FTC and ATC, but not PTC, could harbor LOH in segments of 7q encompassing the loci for HGF and c-met. We screened 6 normal thyroids, 10 colloid nodules, 10 follicular hyperplasias, 10 oncocytic adenomas, 10 follicular adenomas (FA), 10 FTC, 6 ATC, 12 PTC using two microsatellite markers for HGF, and two for c-met. LOH for all 4 markers was found in 100% of FTC, 100% of ATC, and (for only 1 or 2 markers) in 10-29% of FA. This is the first demonstration of an LOH that separates both FTC and ATC from PTC, in the best possible manner: 100% vs. 0%. Clearly, each of the two segments we have probed contains at least one tumor suppressor gene, whose inactivation is crucial for the establishment of the FTC (and ATC) phenotype. This loss of genetic material explains why FTC and ATC, but not PTC, fail to express both HGF and c-met. Our findings may also have immediate diagnostic application, in the context of assisting pathologists in the often difficult task of distinguishing FA from FTC.
Adenocarcinoma, Follicular↗
Testicular adrenal rests: evidence for luteinizing hormone receptors and for distinct types of testicular nodules differing for their autonomization.
We report one patient with 21-hydroxylase deficiency and associated bilateral macro-orchidism caused by nodular hyperplasia of testicular adrenal rests (TAR). The boy, referred to us when 10 years old, was born with bilateral cryptorchidism that was treated unsuccessfully with i.m. injections of human chorionic gonadotropin (hCG) and later on with orchidopexy. He was treated with oral dexamethasone (0.625 mg per day) for the following 13 years. After one year, there was a marked reduction in steroid hormone levels (17-hydroxyprogesterone (17-OH P) from 27.2 to 1.2 nmol/l, testosterone from >104 to 4.8 nmol/l, estradiol (E(2)) from 481 to 33 pmol/l). After the same period of time, both testicular volume and nodularity decreased: from 45 to 18 ml and from numerous to four nodules in the right testis, and from 40 to 13 ml and from numerous to three nodules in the left testis. At the third year, there were transient increases in serum gonadotropins, testicular volume (right testis = 25 ml, left testis = 20 ml) and steroid hormones, including cortisol (serum ACTH and dehydroepiandrosterone sulfate remained suppressed). At the fourth year of follow-up, there were still four nodules in the right testis and three in the left testis. The LH-dependency (which implies possession of LH/hCG receptors) of these nodules was also substantiated by their steroidogenic response to an acute i.m. hCG test. An exogenous ACTH stimulation test increased serum 17-OH P and cortisol. Since these nodules, unlike the majority of those present initially, were not suppressed by the corticosteroid therapy and since they were not detected when the patient returned for control at 23 years of age, they had partial autonomy from ACTH. At 23 years of age, the patient had a single nodule in the right testis (right testis volume = 13 ml, left testis volume = 10 ml), which should have accounted for the consistent difference in size between the two gonads. Serum LH was about 7 mU/l and FSH about 23 mU/l. The responsiveness of plasma steroid hormones to hCG had changed quantitatively and qualitatively. Secretion of cortisol was absent, secretion of 17-OH P and testosterone was reduced, and secretion of E(2) was much increased. The ACTH stimulation test showed that serum cortisol did not respond, while the other steroids responded in the order of 17-OH P>E(2)> testosterone. We conclude that there were three different groups of TAR when the patient was already 10 years old: (i) ACTH-sensitive (the majority), (ii) partially ACTH-insensitive but LH/hCG-sensitive (three nodules in the left testis and three in the right testis), (iii) almost entirely ACTH-insensitive and partially hCG-insensitive (a single nodule in the right testis). Probably, the never suppressed gonadotropin levels (presumably due to the bilateral testicular damage subsequent to the cryptorchid state) and the hCG therapy were major etiological factors for the appearance of the second and third population of TAR.
Adrenal Glands↗
Internal repeats of prion protein and A beta PP, and reciprocal similarity with the amyloid-related proteins.
We are currently interested in a group of proteins associated with the dementias characterized by amyloid deposition in the brain: amyloid beta protein precursor (A beta PP) of Alzheimer's disease (AD) and the abnormal isoform of prion protein (PrP) of spongiform encephalopathies such as kuru, Creutzfeldt-Jacob disease (CJD) and Gerstmann-Straussler-Scheinker disease (GSSD). Here we show that both A beta PP and prion protein (PrP) consist of peculiar internal repeats and share regions of sequence similarity. Further analysis revealed that local homology is also shared with the other proteins involved in specific forms of amyloidosis--i.e., the amyloid related proteins (ARP).
Amino Acid Sequence↗
Thyroid follicular oncogenesis in iodine-deficient and iodine-sufficient areas: search for alterations of the ras, met and bFGF oncogenes and of the Rb anti-oncogene.
To gain insights into the role of iodine deficiency in favoring thyroid tumorigenesis (particularly of the follicular histotype), 22 Sicilian patients with thyroid tumors were selected for having lived permanently in either one of two areas of different iodine availability. Eleven patients (age 46.1 +/- 14.6 years, mean +/- SD; 10 females and 1 male) were from the iodine-deficient (ID) areas of the provinces of Messina and Catania (mean urinary excretion of iodine = 48.1 micrograms/24 hours). Thyroid tumors were follicular or Hürthle cell adenomas (no. = 3), follicular carcinomas (FC, no. = 4), papillary carcinomas (PC, no. = 2) and anaplastic carcinomas (no. = 2). Eleven patients (age 47.1 +/- 15.2 years; 10 females and 1 male) were from the metropolitan area of Messina, an area of relative iodine-sufficiency (IS) (urinary excretion of iodine = 95.2 micrograms/24 hours). These 11 patients had serum levels of TSH that were significantly lower than the corresponding values of the 11 patients from the ID area (0.76 +/- 0.33 vs 1.80 +/- 1.22 mU/l, p = 0.01) The tumors of the 11 patients from the IS area were: follicular or Hürthle cell adenomas (no. = 6), Hürthle cell carcinoma (no. = 1), FC (no. = 2), PC (no. = 2). Molecular biology studies revealed that both the normal as well as the tumor tissue of all 22 patients did not harbor any of the three classical activating mutations (codons 12, 13 and 61) in any of the three ras oncogenes. Similar negative results were obtained as far as loss of heterozygosity of the retinoblastoma (Rb) anti-oncogene is concerned. Immunohistochemistry studies were performed to investigate expression of c-met and basic fibroblast growth factor (bFGF) proto-oncogenes. Only one Hürthle cell carcinoma and the two PC from the IS group, and one FC and the two PC from the ID group stained for the c-met oncogene. Expression of c-met was greater (3+) in the four PC (concerning 70-80% of the tumor cells) than in the other two cancers (1+; < 5% of the tumor cells). In the IS group, positivity for bFGF was detected in 3/6 adenomas, 1/2 FC, the Hürthle cell carcinoma and the two PC. In the ID group, positivity for bFGF was observed in 2/3 adenomas, 2/4 FC, the two PC and the two anaplastic carcinomas. The 8 positive cases from the ID group had a greater level of bFGF expression than the 7 positive cases from the IS group (intensity of staining = 2.0+ vs 1.57+). Interestingly, the greatest expression of bFGF was seen in the cases with peri-tumoral lymphocytic infiltration from either group. In the ID group correlations between (i.) pre-intervention serum TSH and intensity of tumoral staining for bFGF, (ii.) serum TSH and per cent of tumoral cells reactive with anti-bFGF and (iii.) between intensity of staining for bFGF and per cent of tumoral cells bFGF +ve were higher than in the IS group. We conclude that activating mutations of ras, loss of DNA from the Rb locus and over-expression of both c-met and bFGF are of no pathogenetic relevance in driving thyroid tumorigenesis of iodine-deficient areas.
Adult↗
Skeletal muscle disturbances may precede clinical and laboratory evidence of autoimmune hypothyroidism.
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Adolescent↗
Myopathy as the persistently isolated symptomatology of primary autoimmune hypothyroidism.
Although disorders of thyroid function may cause a wide range of muscle disturbances, an overt myopathy has been rarely reported as an isolated clinical presentation of hypothyroidism. We observed 10 patients (5 males and 5 females) who had been referred to the department of neurology because of muscular fatigability, myalgia, cramps, or proximal weakness. Laboratory investigation showed that all patients had hypothyroidism due to Hashimoto's thyroiditis (atrophic variant in 9/10). Classic symptoms/signs of hypothyroidism such as lethargy, constipation, cold intolerance, myxedematous facies, and/or bradycardia were absent, as assessed independently by the three coauthoring thyroidologists. Muscular complaints improved greatly and then disappeared after substitutive levothyroxine treatment. Muscle biopsy revealed nonspecific changes. Nicotinamide adenine dinucleotide reductase (NADH-TR)-hyporeactive cores were present in two patients (10% and 90% of type 1 fibers). On electron microscopy, the core areas showed disorganized myofibrils, Z-band streaming, rod formation, and paucity of mitochondria and glycogen granules. Desmin intermediate filaments were overexpressed only in some cores. The similarity of the pattern of desmin expression between hypothyroid cores and target lesions of denervated fibers supports the hypothesis that, at least in some of our patients, myopathy was the result of an impaired nerve-mediated action of thyroid hormones on skeletal muscle. Our observations suggest that an isolated myopathy as the sole manifestation of hypothyroidism is not a rare event. We postulate that our cases may constitute a peculiar subgroup of Hashimoto's thyroiditis patients: (1) the strikingly abnormal F/M ratio of 1:1; (2) the relatively younger age; (3) the rarity of the goitrous variant; (4) the unusual finding of antithyroglobulin (Tg-Ab) > antithyroid peroxidase (TPO-Ab). Thorough evaluation of thyroid function is appropriate in patients with myopathy of uncertain origin.
Adolescent↗
Expression of the hepatocyte growth factor and c-met in normal thyroid, non-neoplastic, and neoplastic nodules.
We have examined the coexpression of hepatocyte growth factor (HGF) and its receptor (HGF-R or c-met) in an archival series of 63 paraffin-embedded thyroid specimens plus one lymph node metastasis. By immunocytochemistry, we found undetectable expression of both the ligand and the receptor in 10 normal thyroids and 9 nonpapillary malignant nodules [5 follicular carcinomas, 1 poorly differentiated (insular) carcinoma, 3 undifferentiated (anaplastic) carcinomas]. Of 10 non-neoplastic nodules (colloid nodules) and 17 benign neoplastic nodules, 3 of 10 colloid nodules, 2 of 10 follicular adenomas, and 2 of 7 oncocytic adenomas showed a weak but distinct staining (1+ score in a scale from 0 to 4+) of both HGF and c-met in a modest proportion of cells (1% to 3%). In these 7 cases, expression of HGF was always stromal and expression of c-met limited to the membrane of the follicular cells. Of 3 malignant nodules derived from aberrant growth of the parafollicular C cells (medullary thyroid cancer or MTC), 2 were positive (6% of cells). In these 2 cases, the expression of HGF (3+) was not stromal, but in both the membrane and cytoplasm of the parafollicular cells, while that of c-met (3+) was restricted to the membrane. In contrast to all of the above, of 14 papillary carcinomas (PTC) encompassing 5 histological variants (conventional; follicular; oncocytic; with foci of solid growth; diffuse sclerosing) plus 1 neck lymph node metastasis of 1 conventional PTC, 12 (86%) expressed HGF, and 13 (93%) expressed c-met. With the exception of 2 negative cases, HGF was detected in 15% to 46% of the cells. The highest percentage (46%) pertained to conventional PTC cases with abundant peritumoral lymphocyte infiltration, indicating that some lymphokine(s) may recruit PTC cells for HGF expression in a paracrine fashion. With the exception of one negative case, c-met was found in 43% to 80% of the cells, both at levels from intense (3+) to very intense (4+). The immunostaining for HGF was stromal in 25%, membranous in 8%, cytoplasmic in 8%, and both membranous and cytoplasmic in 59% of the PTC-positive cases. The immunostaining for c-met was membranous in 43% and both membranous and cytoplasmic in 57% of the PTC-positive cases. In the lymph node metastasis and in the diffuse sclerosing variant of PTC (the most aggressive variant), the coexpression of HGF/c-met was lost, in that only c-met was expressed on membranes in both cases. We conclude that the HGF/c-met system is activated (by overexpression of both components) in the vast majority of PTC. In most PTC the interaction of HGF and its receptor (c-met) is autocrine, not paracrine.
Carcinoma↗
Thyroid hormone efflux from monolayer cultures of human fibroblasts and hepatocytes. Effect of lipoproteins and other thyroxine transport proteins.
We have previously shown that human skin fibroblasts exposed to preformed low density lipoprotein (LDL)-thyroxine (T4) complexes internalize more T4 than they do when exposed to T4 alone. The system is set to function when the LDL receptor is up-regulated by reducing the intracellular concentration of cholesterol, and the LDL concentration outside the cell is in the range of the kDa of the receptor. High density lipoproteins (HDL), albumin (HSA), transthyretin (TTR), and thyroxine-binding globulin (TBG) interfere with, rather than facilitate, T4 entry. Of the three classes of lipoproteins (VLDL, LDL, and HDL), HDL is the major carrier of thyroid hormones. While LDL delivers cholesterol (and T4) to cells, HDL is the scavenger of cholesterol. We thus hypothesized that HDL could also facilitate thyroid hormone exit from cells. This hypothesis was tested on two human cell lines: skin fibroblasts and hepatocytes (Hep G2), using physiological concentrations of HDL or, as control, physiological concentrations of LDL, HSA, TTR, and TBG or buffer. Because cell surface receptors for HDL are regulated by intracellular cholesterol in a manner opposite to that of LDL receptors, we evaluated the effect of HDL (and other proteins) in three states: normal, high, and low intracellular cholesterol content (i.e. normal, high, and low expression of HDL receptors). In both cell lines and with either T4 or T3, we found that: 1) HDL as well as the other proteins tested increased the efflux and augmented both the initial rate of exit and the equilibrium value. 2) The efflux did not saturate over a wide range of protein concentrations. 3) The effect of HDL, LDL, and the other proteins on the fractional efflux rate of thyroid hormones remained the same irrespective of the intracellular cholesterol content (and, therefore, irrespective of the expression of either LDL or HDL receptors). 4) HSA, TTR, and TBG were, on a mass basis, equipotent and more efficient than lipoproteins. However, the effect of lipoproteins--whose Ka for T4 is comparable to that of HSA--was disproportionately high. On a molar basis, LDL (about 80% of the weight being accounted for by lipids) was more effective than HDL2 (about 60% lipids) and HDL2 was more effective than HDL3 (about 40% lipids), suggesting that the disproportionate effect of lipoproteins was due to transfer of the lypophylic thyroid hormones to the lipid moiety of lipoproteins. 5. A mixture of HDL and LDL gave the same efflux rate as a mixture of HSA, TTR, and TBG. The data indicate that the efflux of T4 and T3 from cells is rapid and appears not to be mediated by a particular lipoprotein. The disproportionately large effect of lipoproteins, which are low affinity thyroid hormone carriers, compared with nonlipoprotein carriers, and the greater effect of LDL compared with HDL, might indicate that the lipoproteins establish a nonspecific physical contact with the plasma membrane and that their hydrophobic nature favors the release of the similarly hydrophobic thyroid hormones.
Carrier Proteins↗
Effect of thyroxine on low density lipoprotein oxidation another thyroid hormone nongenomic effect.
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Humans↗
Thyroid iodide transporter: local sequence homologies with thyroid autoantigens.
Here we show the existence of local amino acid (aa) sequence homologies between rat thyroid iodide transporter (Na+/l- symporter or NIS), whose gene was recently cloned, and known human thyroid autoantigens [thyroglobulin (Tg), thyroid peroxidase (TPO) and thyrotropin receptor (TSHR)] NIS sequences corresponding to the fourth (aa 264-282) and fifth extracellular loop (aa 386-414) are 15 to 40% identical and 30 to 60% similar to sequences corresponding to known or putative epitopes of Tg, TPO and TSHR. The sixth extracellular loop (aa 465-485) beared homology (44% identity, 52% similarity) only to a region of Tg which flanks one of its immunodominant domains. Sequences of thyroid autoantigens other than NIS shared homology, especially Tg and TPO. We conclude that in all likelihood NIS is an additional thyroid antigen, which shares common epitopes with the other thyroid autoantigens. Addendum: A study in abstract form appeared after submission of our paper finds experimental evidence for the antigenicity of two extracellular segments (aa 262-280 and 468-487) and of a portion of the intracellular C-terminus (aa 560-579).
Amino Acid Sequence↗