Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “thyroiditis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,621 records · Page 90Linked to original sources
PubMed1988

Developmental changes in rat brain 5'-deiodinase and thyroid hormones during the fetal period: the effects of fetal hypothyroidism and maternal thyroid hormones.

We have studied the ontogenesis of 5'-deiodinase (5'D) activity in rat brain during fetal life, its capacity to respond to maternal or fetal hypothyroidism, and its regulation by maternal thyroid hormones. Type II 5'D (5' D-II) activity increases 4-fold during the period studied (17 to 22 days of gestation), mainly between days 19 and 21. Fetal brain T4 concentrations increase in parallel with fetal plasma T4, whereas fetal brain T3 concentrations increase 18 times (days 17-21), six times more than would have been expected from the small increase in fetal plasma T3 levels. Maternal thyroidectomy did not affect 5'D-II activity or thyroid hormone concentrations in fetal brain (except brain T4 at 18 days of gestation). Fetal hypothyroidism, induced by giving a goitrogen (methimazole) to the mothers, depleted all fetal tissues studied, including the fetal thyroid, from thyroid hormones. By 19 days of gestation, the fetal brain was able to respond to hypothyroidism with a 3- to 5-fold increase in 5'D-II activity. Earlier onset of treatment with methimazole led to 2- to 3-fold increases in 5'D already at 17 and 18 days of gestation, showing that when fetal thyroid secretion starts the fetal brain 5'D-II is able to respond to hypothyroidism. Replacement of methimazole-treated mothers with physiological doses of T4, given by constant infusion, increased T4 and T3 concentrations in fetal brain, and inhibited fetal, as well as maternal, brain 5'D-II activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Plasma membrane transport of thyroid hormones and its role in thyroid hormone metabolism and bioavailability.

Although it was originally believed that thyroid hormones enter target cells by passive diffusion, it is now clear that cellular uptake is effected by carrier-mediated processes. Two stereospecific binding sites for each T4 and T3 have been detected in cell membranes and on intact cells from humans and other species. The apparent Michaelis-Menten values of the high-affinity, low-capacity binding sites for T4 and T3 are in the nanomolar range, whereas the apparent Michaelis- Menten values of the low-affinity, high-capacity binding sites are usually in the lower micromolar range. Cellular uptake of T4 and T3 by the high-affinity sites is energy, temperature, and often Na+ dependent and represents the translocation of thyroid hormone over the plasma membrane. Uptake by the low-affinity sites is not dependent on energy, temperature, and Na+ and represents binding of thyroid hormone to proteins associated with the plasma membrane. In rat erythrocytes and hepatocytes, T3 plasma membrane carriers have been tentatively identified as proteins with apparent molecular masses of 52 and 55 kDa. In different cells, such as rat erythrocytes, pituitary cells, astrocytes, and mouse neuroblastoma cells, uptake of T4 and T3 appears to be mediated largely by system L or T amino acid transporters. Efflux of T3 from different cell types is saturable, but saturable efflux of T4 has not yet been demonstrated. Saturable uptake of T4 and T3 in the brain occurs both via the blood-brain barrier and the choroid plexus-cerebrospinal fluid barrier. Thyroid hormone uptake in the intact rat and human liver is ATP dependent and rate limiting for subsequent iodothyronine metabolism. In starvation and nonthyroidal illness in man, T4 uptake in the liver is decreased, resulting in lowered plasma T3 production. Inhibition of liver T4 uptake in these conditions is explained by liver ATP depletion and increased concentrations of circulating inhibitors, such as 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, indoxyl sulfate, nonesterified fatty acids, and bilirubin. Recently, several organic anion transporters and L type amino acid transporters have been shown to facilitate plasma membrane transport of thyroid hormone. Future research should be directed to elucidate which of these and possible other transporters are of physiological significance, and how they are regulated at the molecular level.

Animals↗
PubMed1990

Carbohydrate moieties in recombinant human thyroid peroxidase: role in recognition by antithyroid peroxidase antibodies in Hashimoto's thyroiditis.

We studied the oligosaccharide moieties of recombinant human thyroid peroxidase (hTPO) expressed in Chinese hamster ovary (CHO) cells, and the role of these glycans in hTPO antigenicity in Hashimoto's thyroiditis. To determine whether hTPO carbohydrate moieties were N-linked, O-linked, or both, and to obtain information about the characteristics of the carbohydrate component(s), we digested hTPO with deglycosylating enzymes of varying specificity. Proteins in CHO-TPO cells were labeled with [35S]methionine, and hTPO was immunoprecipitated with anti-hTPO antibodies present in Hashimoto's thyroiditis serum. Digestion with endoglycosidase (endo) F, which removes both complex and polymannose N-linked glycans, increased the electrophoretic mobility of the hTPO doublet from approximately 115 kD and 110 kD to 110 kD and 105 kD. Endo H, which acts similarly to endo F, but only on polymannose, and not complex, glycans, had a similar effect. In contrast, O-glycanase and neuraminidase, which remove O-linked glycans and terminal neuraminic acid, respectively, did not alter the mobility of radiolabeled hTPO. Radiolabeled recombinant hTPO was retained by concanavalin A, but not by wheat germ agglutinin, Ricinus communis agglutinin 1, peanut agglutinin and Ulex europaeus lectins. To determine whether or not the glycan moieties in hTPO play a role in the disease-associated epitopes in Hashimoto's thyroiditis, radiolabeled recombinant hTPO was immunoprecipitated after digestion with N-glycanase. Removal of the N-linked carbohydrate chains with endo F and endo H did not prevent antibody binding. In summary, the present data indicate that: i) hTPO expressed in CHO cells contains N-linked, but not O-linked glycan moieties; ii) the N-linked carbohydrate is primarily of the polymannose variety; and, iii) the glycan moieties do not contribute to the hTPO epitopes in Hashimoto's thyroiditis.

Acetylglucosaminidase↗
PubMed1976

Activation of thyroid adenyl cyclase by antisera to thyroid plasma membrane preparations.

Adenyl cyclase was assayed in a series of plasma membrane fractions prepared from bovine thyroids using sucrose density gradient ultracentrifugation. The activity of adenyl cyclase in the plasma membranes was found to be stimulated several-fold by antisera raised in rabbits against the plasma membranes and by purified IgG prepared from these antisera. The data indicate that the antibodies to thyroid plasma membrane manifest properties similar to those of the immunoglobulins long-acting thyroid stimulator (LATS) and human specific thyroid-stimulating immunoglobulin (HTSI) found in patients with Graves' disease. It is suggested that, in these patients, the antigen which leads to the production of LATS and HTSI is most likely situated in the thyroid plasma membrane.

Adenosine Triphosphatases↗
PubMed1993

Ontogeny of thyroid hormone receptors and c-erbA expression during brown adipose tissue development: evidence of fetal acquisition of the mature thyroid status.

We have determined the developmental changes in thyroid hormone receptor expression and thyroid hormone status in rat brown adipose tissue (BAT). The present study demonstrates that c-erbA alpha and -beta genes are expressed in the developing BAT. The 6.5-kilobase (kb) beta 1, 2.6-kb alpha 2, 5.5-kb alpha 1, and 6.6-kb alpha transcripts showed peak values on day 20 of fetal life. High affinity T3-binding sites were found in fetal BAT. Binding capacity was similar (18-day-old fetuses) or higher (20-day-old fetuses) than in postnatal or adult brown fat. In contrast, T3 receptors were scarce in fetal liver, and values in adult liver were similar to those in fetal BAT on day 20. The profiles of iodothyronine 5'-deiodinase, nuclear T3 content, and receptor occupancy also showed peak values in fetal BAT on day 20, but they were very low in fetal liver. Thus, BAT has already achieved complete maturation of its thyroid status on day 20 of gestational age. This highly tissue-specific developmental pattern is unique among other mammalian thyroid-sensitive tissues studied to date. Between days 18 and 20 of rat fetal development, there is a specific induction of the uncoupling protein gene expression, the main marker of differentiated adipocytes. The results suggest that thyroid hormones may be involved in the establishment of the differentiated phenotype of the brown fat cell in fetal life.

Adipose Tissue, Brown↗
PubMed1997

Effects of maternal thyroid status on thyroid hormones and growth in congenitally hypothyroid goat fetuses during the second half of gestation.

Congenital hypothyroidism in Dutch goats is due to a thyroglobulin (TG) synthesis defect that is inherited in an autosomal recessive manner. Minute amounts of mutated TG messenger RNA are translated into glycosylated TG fragments that contain the N-terminal hormonogenic site and are able to form T4, albeit less efficiently. We analyzed the effects of maternal thyroid status on fetal plasma thyroid hormones and growth during the second half of gestation (E90-E150). Maternal hypothyroidism, present from midgestation, resulted in decreased brain and cerebellum weights of affected goitrous fetuses, most evident at term gestation (E150). Brain and cerebellum weights of affected fetuses from unaffected mothers were not decreased. T4 and FT4 levels in affected fetuses were dependent on the maternal phenotype, as was the degree of enlargement of the goiter at E150. Newborn unaffected lambs from affected mothers had plasma T4 levels within the normal range. The present data show that in late gestation, fetal goats have to rely on their own thyroidal T4 production. The results suggest that affected fetuses are able to maintain sufficiently high T4 and T3 levels to prevent severe adverse effects of thyroid hormone deficiency on the brain if maternal iodide supply is adequate, although a possible increased transfer of maternal T4 to affected fetuses cannot be excluded. Under normal conditions, sufficient amounts of iodine are provided by the efficient iodine metabolism in euthyroid mothers. In affected mothers, much iodine is wasted because the thyroid also iodinates proteins other than the aberrant TG, resulting in insufficient iodine provision of the fetus and, consequently, in severe hypothyroidism.

Animals↗
PubMed2001

Dystroglycan is present in rat thyroid and rat thyroid cells and responds to thyrotropin.

Dystroglycan is a high affinity laminin-binding glycoprotein originally described as a member of the dystrophin-associated glycoprotein complex in muscle. We have demonstrated the presence of dystroglycan in the thyroid using immunocytochemistry, immunoblots, ligand binding assays, and relative quantitative RT-PCR. In intact rat thyroid glands, antibodies against the alpha (extracellular, laminin-binding subunit) and beta (cytoplasmic/membrane bound) portions of the dystroglycan protein reacted at basolateral membranes where they colocalized with laminin. Western-blotted protein from the Fischer rat thyroid cell line FRTL-5 reacted with both the alpha- and beta-dystroglycan antibodies. The alpha-dystroglycan-reactive band colocalized with laminin-binding activity, and the protein and binding activity were decreased by TSH. In contrast, in the culture medium of these cells, alpha-dystroglycan was increased by TSH. The beta-dystroglycan antibody recognized the full-length 43-kDa band and an approximately 30-kDa truncated form. The truncated form was reduced in cells cultured with TSH, whereas the full-length form was not significantly diminished by TSH. Immunofluorescence of FRTL-5 cells in the absence of TSH showed a colocalization of dystroglycan and laminin. This was disrupted by the addition of TSH and was correlated to morphological changes. PCR amplification of complementary DNA with primer pairs from alpha- and beta-dystroglycan produced appropriately sized bands, whose sequence had identical protein-coding sequences and more than 96% nucleotide homology to mouse dystroglycan sequences. Relative quantitative RT-PCR of beta-dystroglycan messenger RNA showed reduced expression in cells cultured with TSH. We conclude that dystroglycan is present in rat thyroid and in FRTL5 rat thyroid cells and that TSH reduces its expression.

Animals↗
PubMed2003

Correlation between the loss of thyroglobulin iodination and the expression of thyroid-specific proteins involved in iodine metabolism in thyroid carcinomas.

Progress in biotechnology has provided useful tools for tracing proteins involved in thyroid hormone synthesis in vivo. Mono- or polyclonal antibodies are now available to detect on histological sections the Na(+)/I(-) symporter (NIS) at the basolateral pole of the cell, the putative iodide channel (pendrin) at the apical plasma membrane, thyroperoxidase (TPO), and members of the NADPH-oxidase family, thyroid oxidase 1 and 2 (ThOXs), part of the H(2)O(2)-generating system. The aim of this study was to correlate thyroglobulin (Tg) iodination with the presence of these proteins. Tg, T(4)-containing Tg, NIS, pendrin, TPO, ThOXs, and TSH receptor (TSHr) were detected by immunohistochemistry on tissue sections of normal thyroids and various benign and malignant thyroid disorders. Tg was present in all cases. T(4)-containing Tg was found in the adenomas, except in Hurthle cell adenomas. It was never detected in carcinomas. NIS was reduced in all types of carcinomas, whereas it was detected in noncancerous tissues. Pendrin was not expressed in carcinomas, except in follicular carcinomas, where weak staining persisted. TPO expression was present in insular, follicular carcinomas and in follicular variants of papillary carcinomas, but in a reduced percentage of cells. It was below the level of detection in papillary carcinomas. The H(2)O(2)-generating system, ThOXs, was found in all carcinomas and was even increased in papillary carcinomas. Its staining was apical in normal thyroids, whereas it was cytoplasmic in carcinomas. The TSHr was expressed in all cases, but the intensity of the staining was decreased in insular carcinomas. In conclusion, our work shows that all types of carcinomas lose the capacity to synthesize T(4)-rich, iodinated Tg. In follicular carcinomas, this might be due to a defect in iodide transport at the basolateral pole of the cell. In papillary carcinomas, this defect seems to be coupled to an altered apical transport of iodide and probably TPO activity. The TSHr persists in virtually all cases.

Biomarkers↗
PubMed2003

Recombinant human thyrotropin reduces serum vascular endothelial growth factor levels in patients monitored for thyroid carcinoma even in the absence of thyroid tissue.

In this study, we have investigated in vivo the time-dependent effects of TSH on vascular endothelial growth factor (VEGF) production in patients monitored for thyroid carcinoma. Serum VEGF, thyroglobulin (Tg), and TSH levels were assayed at baseline and 6, 24, 30, 48, 72, and 96 h and 1 wk after administration of recombinant human TSH (rhTSH) in 45 thyroidectomized patients affected by differentiated thyroid carcinoma. At baseline, the patients with metastasis (18 cases) showed serum Tg and VEGF values significantly higher than those seen in the cured patients (27 cases). During rhTSH stimulation, the mean VEGF levels decreased significantly in both patient groups. In 60% of patients with metastasis, VEGF nadir occurred at the same time as serum TSH reached the highest values, whereas in 85.7% of the cured patients VEGF decreased after the TSH peak (P = 0.003). In conclusion, we demonstrate for the first time that short-term administration of rhTSH in patients monitored for differentiated thyroid carcinoma induces a significant reduction in serum VEGF values even in the absence of thyroid tissue. This result would suggest that TSH may be able in vivo to regulate VEGF production from tissues other than the thyroid gland.

Adult↗
PubMed2004

Aurora B overexpression associates with the thyroid carcinoma undifferentiated phenotype and is required for thyroid carcinoma cell proliferation.

Alterations in chromosome number (aneuploidy) are common in human neoplasias. Loss of mitotic regulation is believed to induce aneuploidy in cancer cells and act as a driving force during the malignant progression. The serine/theronine protein kinases of aurora family genes play a critical role in the regulation of key cell cycle processes. Aurora B mediates chromosome segregation by ensuring orientation of sister chromatids and overexpression of Aurora B in diploid human cells NHDF (normal human diploid fibroblast) induces multinuclearity. We analyzed Aurora B expression in human thyroid carcinomas. Cell lines originating from different histotypes showed an increase in Aurora B expression. Immunohistochemical analysis of archive samples showed a high expression of Aurora B in anaplastic thyroid carcinomas; conversely, Aurora B expression was not detectable in normal thyroid tissue. Real-time PCR analysis confirmed a strong expression of Aurora B in anaplastic thyroid carcinomas. The block of Aurora B expression induced by RNA interference or by using an inhibitor of Aurora kinase activity significantly reduced the growth of thyroid anaplastic carcinoma cells.

Animals↗
PubMed2005

Osteopontin is overexpressed in human papillary thyroid carcinomas and enhances thyroid carcinoma cell invasiveness.

UNLABELLED: The transmembrane glycoprotein CD44v6 is overexpressed in most papillary thyroid carcinomas (PTC). We previously reported that osteopontin (OPN), a secreted glycoprotein that functions as a ligand for CD44v6, is overexpressed in thyrocytes transformed by the RET/PTC oncogene. OBJECTIVE: In this study we asked whether OPN is overexpressed in human PTC samples, and whether its expression correlates with clinical and histological features of the tumors. Furthermore, we wanted to establish the functional role of the CD44-OPN axis in thyroid tumorigenesis. DESIGN: Thyroid samples from 117 patients who had undergone surgical resection of the thyroid gland for benign or malignant lesions were collected. OPN and CD44 expressions were evaluated by immunohistochemistry with specific monoclonal antibodies. OPN expression was correlated with different PTC histological variants, lymph node metastasis, and PTC size. RESULTS: In this study we show that OPN is overexpressed in human PTCs with respect to normal thyroid tissue, follicular adenomas, and multinodular goiters (P < 0.05). The prevalence and intensity of OPN staining were significantly correlated with the presence of lymph node metastases (P = 0.0091) and tumor size (P = 0.0001). We also show that treatment of human PTC cells with recombinant exogenous OPN stimulated Matrigel invasion and activated the ERK and V-AKT murine thymoma viral oncogene homolog 1/protein kinase B; signaling pathways. Blockage of anti-CD44 antibodies prevented these effects. CONCLUSIONS: Given its prevalence and its correlation with aggressive features of human PTCs, we suggest that OPN might be used as a diagnostic and prognostic marker for these tumors. Furthermore, given the role of the OPN-CD44v6 axis in PTC cells, we suggest that CD44 and/or OPN may be molecular targets for therapeutic intervention in aggressive PTCs.

Carcinoma, Papillary↗
PubMed1981

Absence of thyroid-stimulating antibody and long acting thyroid stimulator in relatives of Graves' disease patients.

None of the 76 euthyroid relatives of patients with Graves' disease had detectable LATS in their serum nor was thyroid-stimulating antibody (TSAb), assessed by an increment of cAMP in human thyroid slices, detected in any of the 60 sera tested. Seven of 41 were slightly positive for TSH binding-inhibiting immunoglobulin (TBII). Nineteen of 73 sera were positive (greater than 1:1600) for antibody to thyroid antimicrosomal antigen, of which 4 were also positive (greater than 1:400) for antibody to thyroglobulin; 3 of the 19 had a slightly elevated basal TSH which rose excessively after TRH. Thus, although these euthyroid relatives had evidence of thyroid immunological defects, a thyroid-stimulating antibody was not found.

Antibodies↗
PubMed1988

Thyroglobulin and thyroid peroxidase share common epitopes recognized by autoantibodies in patients with chronic autoimmune thyroiditis.

Monoclonal antibodies specific for human thyroid peroxidase (TPO) were prepared by the hybridoma technique using hyperimmune spleen cells from mice immunized with TPO purified from thyroid glands from patients with Graves' disease. Use of the microenzyme-linked immunosorbent assay method revealed that some of the monoclonal antibodies cross-reacted strongly with human thyroglobulin (Tg). Conversely, monoclonal anti-Tg antibodies cross-reacted with TPO, albeit to a lesser degree. Some anti-Tg autoantibodies in serum from patients with chronic autoimmune thyroiditis purified by Tg affinity chromatography bound TPO, and such binding was completely inhibited by Tg. Western blotting experiments revealed that thyroid microsomal 103K proteins recognized by mouse monoclonal and polyclonal anti-TPO antibodies were recognized by some monoclonal anti-Tg antibodies and anti-Tg autoantibodies, and conversely, that 19S Tg was recognized by some monoclonal anti-TPO antibodies. TPO was immunoprecipitated by anti-Tg autoantibodies isolated by Tg affinity chromatography. On the other hand, the specificity for TPO of the anti-Tg autoantibodies was not identical with that of anti-TPO autoantibodies. These cross-reactivities were not due to contamination of TPO with Tg or vice versa, or to contamination of the anti-Tg autoantibody preparations with anti-TPO autoantibodies. Taken together, these data indicate that Tg and TPO share common antigenic determinants and that some of those determinants are recognized by autoantibodies in the serum of patients with chronic autoimmune thyroiditis.

Adolescent↗
PubMed1989

Regulation of thyroid peroxidase and thyroglobulin gene expression by thyrotropin in cultured human thyroid cells.

cDNAs for thyroid peroxidase (TPO) and thyroglobulin (Tg) have been cloned and sequenced. Using such cDNAs, we investigated the regulation of TPO and Tg gene expression by various agents in cultured human thyroid cells. Unstimulated human thyroid cells contained a major RNA species [3.2 kilobases (kb) in length] and several minor RNA species (less than 3.2 kb mRNA) of TPO, but no detectable Tg transcripts. However, TSH-stimulated thyroid cells contained four distinct TPO mRNA species (4.0, 3.2, 2.1, and 1.7 kb) and a single Tg mRNA species (8.5 kb). TSH stimulated the TPO and Tg mRNA levels in a dose- and time-dependent manner. The same results were obtained with 8-bromo-cAMP, a cAMP analog, but not with insulin or insulin-like growth factor I. Furthermore, inductions of these mRNAs by TSH and 8-bromo-cAMP were almost completely blocked by cycloheximide, a protein synthesis inhibitor. These results suggest that human thyroid cells contain four distinct TPO mRNAs and a single species of Tg mRNA, and the levels of all mRNAs are increased by TSH/cAMP stimulation. These increases are blocked by inhibiting protein synthesis, indicating that TSH stimulation of TPO and Tg mRNA levels may be mediated by newly synthesized protein(s).

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1990

Susceptibility to thyroid autoimmune disease: molecular analysis of HLA-D region genes identifies new markers for goitrous Hashimoto's thyroiditis.

Hashimoto's thyroiditis has been shown to be associated with the HLA-specificities DR4 and DR5. Since former association studies yielded variable results, we used novel molecular typing methods to assess predisposing immunogenetic factors. Gene analysis of the HLA-DR-DQ and tumor necrosis factor region was performed in a group of Hashimoto's thyroiditis patients and randomly chosen controls using standards and nomenclature of the 10th International Histocompatibility Workshop. Genomic DNA of patients and controls was analyzed using a cDNA probe of the DQB1 gene. The resulting restriction fragment patterns allowed the determination of newly defined DQw-types 1-9. We find the strongest relative risk conferred by DQw7 (RR = 4.7), that is observed in 36 of 64 patients (56%) and only 21 of 98 controls (21%) (P corr less than 0.002). Comparison of DNA sequence variation in the DQB1 gene, that is found predominantly in Hashimoto's thyroiditis patients, indicates that codons 45 and 57 are critical features in DQw7 which distinguish it from other DQw specificities. The adjacent DQA1 genes also display a significant association with Hashimoto's thyroiditis (DQA1*0201/*0301 heterozygotes were found in 37% of patients and 15% controls, P less than 0.03). No significant association could be found with polymorphisms of the tumor necrosis factor gene. These results provide a new basis for the concept of genetic susceptibility in Hashimoto's thyroiditis and will help to elucidate the underlying autoimmune mechanisms that lead to disease at the functional level.

Amino Acid Sequence↗
PubMed1991

Autosomal dominant inheritance of autoantibodies to thyroid peroxidase and thyroglobulin--studies in families not selected for autoimmune thyroid disease.

Recently the tendency to produce autoantibodies to thyroid peroxidase (TPO Ab) and thyroglobulin (Tg Ab) was shown to be inherited as an autosomal dominant characteristic in women but not in men. Because of potential bias in this study which was carried out in families with autoimmune thyroid disease (AITD), the inheritance of thyroid autoantibodies has been evaluated in 49 families unselected for autoimmune thyroid disease. Among these families (24 with facioscapulohumeral disease, 10 with Friedreich's ataxia, and 15 with schizophrenia) the prevalences of TPO Ab and Tg Ab were 27.8% and 26.7%, respectively, in women and 9.2% and 11.7%, respectively, in men. In 40 families where one or more individual had TPO Ab and/or Tg Ab, segregation analysis showed that the tendency to make antibodies was consistent with a Mendelian dominant trait in women but not in men. In young women, however, the prevalence of both TPO Ab and Tg Ab increased with age, rising from 14% and 10%, respectively, at age 15-24 to 35% and 40% at age 35-44. As this is inconsistent with a simple dominant hypothesis, a further segregation analysis by age was carried out in the families unselected for thyroid disease together with 16 pedigrees with AITD previously studied and two additional large AITD families. The results of the combined analysis provided strong support for the hypothesis of dominant inheritance but also showed significant reduction in gene expression among women aged 15-24 yr.

Adolescent↗
PubMed1991

Recombinant human thyroid-stimulating hormone: initial bioactivity assessment using human fetal thyroid cells.

We have assessed the bioactivity of newly available recombinant human TSH (rec-hTSH) using human fetal thyroid cells, with the longer term aim of assessing its use for clinical applications. Rec-hTSH caused a consistent and dose-related increase in thyroid monolayer cell cAMP release and human thyroglobulin (hTg) secretion, confirming its bioactivity. Repetitive studies (n = 5) allowed us to derive an estimated biopotency for the rec-hTSH preparation examined of 5.6 IU/mg compared to 10 IU/mg for commercially available bovine TSH for human use. The rec-hTSH had a bioimmune ratio of 0.55, similar to that of purified pituitary hTSH standards, Furthermore, rec-hTSH induced thyroid epithelial cell growth, as evidenced by a decrease in thyroid cell doubling time from 54 +/- 2.1 to 31 +/- 1.7 h (P less than 0.005). Hence, rec-hTSH is a potent glycoprotein hormone preparation when measured in a homologous human thyroid cell culture system. Rec-hTSH could serve as a future definitive International Standard and has the potential for a useful diagnostic and therapeutic reagent.

Cell Division↗
PubMed1991

Pregnancy-induced changes in thyroid function: role of human chorionic gonadotropin as putative regulator of maternal thyroid.

Marked changes in maternal thyroid activity occur in pregnancy. It has been suggested that hCG may stimulate maternal T4 secretion, given its in vitro thyrotropic activity ascribed to a significant degree of structural homology with TSH. In a longitudinal study of 32 normal pregnant women, we attempted to clarify the functional activity of the thyroid in early and late pregnancy and the possibility of a nonpituitary control on the thyroid. Total T4 and T4-binding globulin levels were increased from the first trimester onward. Free T4 levels did not differ in the first trimester from postpartum values, but were significantly decreased in second and third trimesters (P less than 0.001). A decrease in TSH levels was observed in the first trimester (0.72 +/- 0.09 vs. 1.23 +/- 0.12 mU/L; P less than 0.001), while second and third trimester values did not differ from those postpartum. A significant negative correlation (P less than 0.05) was observed between hCG and TSH levels in the earliest weeks (8-10) of the first trimester. No correlation was found between hCG and total T4 or free T4 levels. A stimulation of I- uptake in FRTL-5 cells was induced by first trimester serum, which also showed a different behavior at chromatofocusing, with a higher proportion of hCG eluting at acidic pIs compared to second trimester samples. However, neither hCG levels nor the amount of acidic hCG correlated with the thyroid-stimulating activity measured in vitro. Some correlation was found with the percentage of basic hCG (eluting at pI greater than 4.6), although these isoforms were equally present in first and second trimesters. The differing patterns of circulating hCG at various stages of gestation suggest that distinct hCG isoforms may regulate maternal thyroid activity.

Chorionic Gonadotropin↗