PubMed Health⌕ Search

Biomedical subjects

S Filetti

Publications and source records attributed to S Filetti.

At least 19 recordsLinked to original sources
PubMed1991

Lack of relationship between 3',5'cyclic adenosine monophosphate desensitization and thyrotropin receptor down regulation in the rat thyroid cell line FRTL5.

We studied the cAMP response and radioiodinated TSH binding in the FRTL5 rat thyroid cell line after chronic exposure to TSH. In parallel experiments, continuous exposure to TSH induced both a decrease in the cellular cAMP responsiveness to a second acute stimulation by thyrotropin (desensitization) and a reduction in 125I-TSH cellular binding (down-regulation). These two processes appeared to differ in that: a) cAMP desensitization was maximal (45-55% inhibition in comparison to control cells) after 24 h of preexposure to TSH; on the contrary, a loss of the TSH binding to thyroid cells was detected only after 24 h and was maximal (55-65% lower than control cells) after 48 h of preexposure to TSH; b) a different dependence on the TSH dose was observed for cAMP desensitization and TSH down-regulation: the former was maximal at 10 microU/ml of TSH, the latter only at 10 mU/ml of TSH; c) recovery from cAMP desensitization was detected 3 h after TSH withdrawal and was fully achieved at 24 h, whereas the recovery from the TSH receptor down-regulation was not evident for up to 24 h and a full recovery obtained only at 72 h; d) the use of cAMP analogues proved that, unlike desensitization, TSH receptor down-regulation is a cAMP dependent process. These findings support the concept that different patterns of response to prolonged stimulation with TSH, an earlier and cAMP-independent process (desensitization) and a later cAMP-dependent mechanism (down-regulation), occur in the rat thyroid cell.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

Recombinant human thyrotropin (TSH) receptor in a radioreceptor assay for the measurement of TSH receptor autoantibodies.

We studied the suitability of using the recombinant human TSH receptor expressed in Chinese hamster ovary cells in a TSH binding inhibition (TBI) assay for autoantibodies against the TSH receptor. Purified immunoglobulin G (IgG) containing potent thyroid-stimulating immunoglobulin bioactivity competed for radiolabeled TSH binding to recombinant TSH receptor in parallel to inhibition by unlabeled TSH. Using polyethylene glycol-prepared IgG, this assay discriminated very well between sera from normal individuals [TBI, 0.98 +/- 0.04 (+/- SD); range, 0.92-1.08; n = 35] and patients with untreated Graves' disease (TBI, 0.49 +/- 0.23; range, 0.06-0.98; n = 93). Only four of the sera from the untreated Graves' patients were TBI negative (greater than or equal to 0.92), providing a sensitivity of 96%. In sera from patients with Graves' disease receiving antithyroid drug therapy, TBI was 0.63 +/- 0.18 (range, 0.19-0.97; n = 75). In this group of treated patients, 2 of 75 were TBI negative. Four of 12 patients with Hashimoto's thyroiditis (33%) were positive for TBI activity. All 18 patients with nonautoimmune thyroid diseases (toxic nodular goiter, single toxic adenoma, subacute thyroiditis, or thyroid cancer) were TBI negative. Correlation of the TBI values with thyroid-stimulating immunoglobulin bioactivity revealed a generally positive correlation (r = 0.31; P less than 0.05); however, there were many discrepancies among individual sera. TSI bioactivity was undetectable in all 4 patients with Hashimoto's thyroiditis who were TBI positive. These data indicate that the recombinant TSH receptor in Chinese hamster ovary cells is a suitable system for detecting TBI activity in the sera of patients with autoimmune thyroid disease.

Animals↗
PubMed1991

The biological activity of bovine and human thyrotropin is differently affected by trypsin treatment of human thyroid cells: thyroid-stimulating antibody is related to human thyrotropin.

Pretreatment of cultured human thyroid cells with trypsin decreased the cAMP response to bovine TSH (bTSH) (by 50-60%). In striking contrast, in trypsin treated cells the cAMP stimulation by both human TSH (hTSH) and thyroid-stimulating antibodies (TSab) was unimpaired, indicating a similar behavior for these two stimulators. The effect of trypsin on inhibiting cAMP stimulation by bTSH was: 1) dose dependent; 2) present at a trypsin concentration as low as 3.3 mg/L; 3) fully reversible within 24 h after removal of the enzyme. In accordance with the altered biological activity in human thyroid cells exposed to trypsin the binding of labeled bTSH was reduced (about 40%). On the contrary, in the same cells, the binding of labeled human TSH was enhanced (about 3-fold). The cAMP response to cholera toxin and forskolin was unaffected in trypsin treated cells, indicating that the tryptic treatment did not alter any other component of the adenylate cyclase complex. The medium obtained from trypsin-treated human thyroid cells was able to neutralize the biological activity of bTSH but not that of hTSH or TSab. Our study demonstrates that in human thyroid cells: 1) trypsin impaires bovine, but not human TSH or TSab biological activity; 2) bovine and human TSH may bind to different components of the TSH receptor.

Animals↗
PubMed1990

Effect of thyrotropin and cAMP on FRTL5 cell growth in a serum free medium.

TSH-induced proliferation of FRTL5 cells was studied in a chemically serum-free, defined medium. FRTL5 cells incubated for several days in a medium lacking of serum and hormones were fully able to respond to TSH in terms of cAMP production and iodine uptake. In the same medium, TSH stimulated FRTL5 cell growth as assessed by thymidine incorporation, DNA content and cell count. In these experimental conditions the cellular doubling time was of 7.5 days as compared to 40 h when calf serum was present together with TSH. Cholera toxin, forskolin and (bu)2cAMP, substances able to selectively increase intracellular cAMP levels, were not as efficient as TSH in inducing FRTL5 cell growth. However, both TSH and (bu)2cAMP, in a similar way, induced c-myc gene expression and cellular progression through the prereplicative phase of cell division. These data demonstrate that cAMP-dependent mechanisms are only partially responsible for TSH-induced FRTL5 cell growth, thus suggesting a role of cAMP-independent mechanisms.

Animals↗
PubMed1990

Recombinant human thyroid peroxidase generated in eukaryotic cells: a source of specific antigen for the immunological assay of antimicrosomal antibodies in the sera of patients with autoimmune thyroid disease.

Recombinant, enzymatically active human thyroid peroxidase (hTPO) generated in nonthyroidal eukaryotic cells was compared with Graves' thyroid microsomes as a source of antigen for the immunological detection of antimicrosomal/anti-hTPO antibodies. Enzyme-linked immunosorbent assay of 51 sera, selected to produce a balanced distribution of antimicrosomal antibody (anti-MSA) levels, revealed (at 1:100 serum dilution) a moderately good correlation between anti-MSA and anti-hTPO antibody levels (r = 0.668; P less than 0.001). However, a number of sera with high anti-MSA levels yielded markedly discordant values between the two assays. A much lower correlation was observed between antithyroglobulin and anti-hTPO antibody levels (r = 0.315; P less than 0.05). At higher serum dilutions (1:1,000 and 1:10,000), at which low affinity, high capacity binding reactions will be reduced, the correlation between anti-MSA and anti-hTPO antibody values was greatly improved (r = 0.906 and 0.902, respectively; P less than 0.001), and there were no longer widely discrepant values between the two assays. In summary, the present study indicates that recombinant hTPO expressed in nonthyroidal cells provides an unlimited source of human TPO of unvarying quality for anti-hTPO antibody assays. This material offers increased specificity over standard anti-MSA assays that use thyroid cell microsomes as antigen.

Antigen-Antibody Reactions↗
PubMed1990

Increased aggressiveness of thyroid cancer in patients with Graves' disease.

To evaluate whether coexistence of Graves' disease affects the prognosis of thyroid cancer we examined the clinical and pathological characteristics of 22 differentiated thyroid carcinomas concomitant with hyperthyroidism; 13 were associated with Graves' disease, and 9 with autonomous thyroid nodules. Carcinomas were identified in a consecutive series of 359 hyperthyroid patients (132 with Graves' disease and 227 with autonomous thyroid nodules) who underwent surgery during a 6-yr period. One hundred and thirty-seven thyroid carcinomas were found in the 582 euthyroid patients operated on in the same period. In Graves' patients, carcinomas were more often multifocal (46.1% vs. 0%), locally invasive (61.5% vs. 11.1%), and metastatic to lymph nodes (61.5% vs. 11.1%) or to distant sites (23.0% vs. 0%) than in patients with autonomous thyroid nodules. In addition, carcinomas concomitant with Graves' disease were larger (3.3 +/- 1.8 vs. 1.0 +/- 0.7 cm) than the ones associated with autonomous thyroid nodules and showed a high recurrence rate. In euthyroid patients, aggressiveness of thyroid cancer was intermediate. Serum TSH levels were suppressed in all hyperthyroid patients with thyroid cancer. However, circulating thyroid-stimulating antibodies were present in 12 of 13 cancer patients with Graves' disease, but were absent in patients with autonomous thyroid nodules. Our study suggests, therefore, that TSAb may play a role in determining the high aggressiveness of thyroid cancer in Graves' disease patients and indicates that a vigorous treatment should be pursued in this subgroup of patients.

Graves Disease↗
PubMed1989

Thyrotropin regulation of thyroid peroxidase messenger ribonucleic acid levels in cultured rat thyroid cells: evidence for the involvement of a nontranscriptional mechanism.

The influence of TSH on thyroid peroxidase (TPO) gene expression was investigated in FRTL5 rat thyroid cells. Cultured in the presence of TSH, these cells express a TPO mRNA species of 3.1 kilobases. TSH withdrawal from the culture medium led to a decline in TPO mRNA levels over 24 h. In contrast, no decline in beta-actin mRNA levels occurred after 24 h of incubation in TSH-free medium. TSH (1 mU/ml) added to FRTL5 cells cultured in the absence of TSH increased TPO mRNA levels 7- to 9-fold compared to levels in control cells. This effect of TSH on TPO mRNA accumulation in FRTL5 cells was time related (it was already present after 4 h and was maximal after 24 h of cell exposure to TSH), dose related (0.01 and 1 mU/ml were, respectively, the lowest and the maximally effective doses), and independent of new protein synthesis, in that it was not prevented by cycloheximide (100 microM). cAMP analogues [8-bromo-cAMP and (Bu)2cAMP] also increased TPO mRNA levels, although to a lesser degree than TSH. Run-on transcription analysis in nuclei prepared from FRTL5 cells previously cultured in the presence or absence of TSH did not reveal any difference in TPO mRNA transcripts. These results suggest that TSH regulates the level of TPO mRNA in FRTL5 cells, in part via the second messenger cAMP and by a nontranscriptional mechanism. This TSH effect may represent a primary site of TSH action in regulating TPO bioactivity.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1989

High frequency of cancer in cold thyroid nodules occurring at young age.

In order to evaluate the risk of malignancy of cold thyroid nodules occurring in young as compared with adult patients, we studied a consecutive series of 2327 patients with a solitary cold thyroid nodule over a 6-year period. None of these patients had been previously irradiated in the neck or head. Fine needle aspiration of the nodule and cytologic examination were carried out in all patients and, on the basis of this evaluation and clinical examination 391 patients were selected for surgery; 109 patients were 4-20 years old and 2218 patients were older than 20 years. Malignancy was found in 11 (10.1%) and in 112 (5.0%) of cold thyroid nodules occurring in young and adult patients, respectively. The annual incidence of cold thyroid nodules in the population of the area studied was 5.2 vs 55.9 (per 10(5) inhabitants) in the young and in the adult group, respectively, and the annual incidence of thyroid cancer was 0.53 vs 2.82 (per 10(5) inhabitants) in the young and in the adult patients, respectively. The present study indicates, therefore, that in the absence of head or neck irradiation, cold thyroid nodules are much less frequent in young age, but that the malignancy rate of cold nodules occurring in young patients is 2-fold higher than in adults patients.

Adolescent↗
PubMed1987

The functional activity of the rat c-Ha-ras promoter requires the coordinate involvement of multiple elements.

Promoter activity in the rat c-Ha-ras promoter region was assessed in NIH 3T3 cells using the chloramphenicol acetyltransferase (CAT) reporter gene. Promoter activity was orientation dependent. Deletion of the GC box closet to the transcriptional start site, or the upstream GC box and the two CAAT boxes, greatly diminished promoter activity. The GC boxes in the SV40 early promoter could not functionally replace the downstream c-Ha-ras GC box, but specifically competed for expression of rat c-Ha-ras promoter activity. Serum-stimulated growth of 3T3 cells stably transfected with p035-ras-CAT was not associated with increased promoter activity. These data indicate that the GC and CAAT boxes in the rat c-Ha-ras gene are related to constitutive, and not regulatory, promoter activity, and that these elements are involved in a coordinate manner.

Acetyltransferases↗
PubMed1987

Desensitization of the thyroid cyclic AMP response to thyroid stimulating immunoglobulin: comparison with TSH.

Studies were conducted to examine the characteristics of thyroid cell cAMP stimulation by thyroid stimulating immunoglobulins (TSI) and to compare the cAMP response to TSI and TSH in desensitized human thyroid cells. In terms of cAMP production, preexposure (eight hours) of the cells to TSI induced a desensitization very similar to TSH-induced desensitization: both TSH- and TSI-desensitized cells showed a normal response to cholera toxin and forskolin stimulation; TSH and TSI desensitization was interchangeable in that desensitization by either stimulator affected the action of the other; the time of recovery from either TSH and TSH desensitization was identical; the cycloheximide (10(-4) mol/L) prevented both TSI- and TSH-induced desensitization; preexposure of the cells to iodine, which affects mainly the adenylate cyclase catalytic unit, or to epinephrine, which activate the inhibitory regulatory protein Ni by the alpha 2-adrenergic stimulation, induced a similar inhibition of the subsequent stimulation by both TSH or TSI. The remarkable similarities between TSH and TSI in stimulating and desensitizing thyroid cells strongly support the concept that TSI activates thyroid adenylate cyclase by interacting with the TSH receptor and not through an allosteric mechanism.

Cells, Cultured↗
PubMed1987

Insulin binding and biological activities in the FRTL-5 rat thyroid cell line.

A cloned rat thyroid cell line (FRTL-5) was examined for both insulin binding and responsiveness. The characteristics of insulin binding to thyroid cells were similar to those observed in typical insulin target cells. The 125I-insulin binding was time and temperature dependent and Scatchard analysis suggested the presence of two major binding sites with high and low affinity constant (Kd = 1.4 X 10(-10) mol/L and 1.5 X 10(-9) mol/L, respectively). 125I-insulin was also internalized and degraded in a temperature-dependent manner. IGF1 was weakly effective in completing 125I-insulin binding to FRTL-5 cells (57% inhibition at 333 nmol/L), whereas noninsulin-related peptide hormones were ineffective. Exposure of FRTL-5 cells to insulin stimulated both methyl-aminoisobutyric acid (M-AIB) and 2-deoxy-D-glucose (2DG) transport. These effects were evident at 10(-9) mol/L and maximal at 10(-7) mol/L insulin. Maximal stimulation was three- to four-fold over basal value for both M-AIB and 2DG transport. These data suggest that insulin specifically binds to FRTL-5 cells and regulates different biological functions of this thyroid cell line.

Aminoisobutyric Acids↗
PubMed1987

Nucleotide sequence and characterization of the 5' flanking region of the rat Ha-ras protooncogene.

Thyrotropin and cAMP stimulate growth of FRTL5 rat thyroid cells and increase c-Ha-ras mRNA levels. To study the mechanism by which thyrotropin enhances c-Ha-ras expression in the thyroid, we constructed a genomic library of FRTL5 DNA in the bacteriophage vector EMBL3. Using a v-Ha-ras probe (0.7-kilobase Sst I-Pst I fragment), we isolated eight clones containing portions of the FRTL5 c-Ha-ras gene. Restriction mapping of one of these clones revealed a structure very similar to that previously reported for the rat c-Ha-ras gene. We determined the nucleotide sequence of exon 1 as well as 1.15 kilobases upstream from exon 1. Blot-hybridization analysis of FRTL5 thyroid cell mRNA was performed with three DNA fragments upstream of exon 1. Two of these probes were Pst I-Pst I fragments 0.4 and 0.55 kilobases long, 1.15 and 0.6 kilobases upstream of exon 1, respectively. The third probe, a 0.6-kilobase Pst I-HindIII fragment, was immediately upstream of exon 1 and included 54 base pairs of the 5' end of exon 1. The data revealed an upstream ("-1") exon, consistent with the homology between the nucleotide sequences of our clone and the human c-Ha-ras gene in this region. Primer extension of a synthetic 30-mer oligonucleotide probe complementary to exon +1 on a FRTL5 mRNA template revealed three transcription start (cap) sites, 182, 169, and 153 bases upstream of the ATG codon. "CCAAT boxes" are present 65 and 100 bases upstream from the initial cap site. Three "GC boxes" and two C + G-rich inverted repeats characteristic of the binding site for the transcription regulation factor Sp1 are present in the 177 base pairs upstream of the initial cap site. Comparison of the rat and human c-Ha-ras -1 exons showed an area of poor homology immediately upstream of the human cap sites, followed further upstream by a region of close homology (approximately equal to 60 base pairs). The nucleotide sequence of the rat -1 exon is more similar to the v-ras sequence than is the human. The v-ras gene is truncated relative to both human and rat -1 exons.

Amino Acid Sequence↗
PubMed1987

Thyrotropin stimulates glucose transport in cultured rat thyroid cells.

Glucose transport by FRTL-5 cells, a rat thyroid cell line, was found to be TSH dependent. The effect of TSH on the uptake of 2-deoxy-D-glucose, a nonmetabolizable glucose analogue, was prompt, being 200% over basal value after 10 min and maximal after 12 h (600-700% increase). The TSH effect was dose dependent, with half-maximum stimulation at 10 microU TSH/ml, and maximum stimulation at 1 mU TSH/ml. TSH enhanced also the uptake of 3-O-methyl-D-glucose by FRTL-5 cells. The TSH activation of glucose transport had the following characteristics: it was mimicked by (Bu)2-cAMP (1 mM) and by agents that increase cAMP levels in thyroid cells, such as forskolin (10 microM) and cholera toxin (50 micrograms/ml); it involved the facilitated glucose transport system in that it was inhibited in a dose-related manner by both cytochalasin B and phloretin; it showed a glucose stereochemical sensitivity, being affected by D-glucose and 3-O-methyl-glucose, and not by L-glucose; it was characterized by an increase in the maximum velocity (Vmax) of glucose uptake (from 15.3 to 66.0 fmol/min X micrograms DNA) without change in the Michaelis-Menten constant (Km) (5.3 mM); the effect on the Vmax was due to an increase in the number of surface glucose transporters as indicated by the enhancement of the D-glucose-sensitive fraction of [3H]cytochalasin B binding sites that in thyroid plasma membranes of cells exposed to TSH for 2 and 8 h, increased from 5.0 (basal value) to 10.4 and 23.1 pmol/mg protein, respectively. These data indicate that in FRTL-5 cells TSH stimulates the glucose transport system by an enhancement of the number of functional glucose transporters in the thyroid plasma membrane.

3-O-Methylglucose↗
PubMed1987

Treatment of neonatal hyperthyroidism due to Graves' disease with sodium ipodate.

We describe the effect of administration of repeated doses of sodium ipodate in a newborn infant with hyperthyroidism due to transient Graves' disease. Pretreatment (day 3) serum T4 and T3 concentrations were 49 micrograms/dl and 590 ng/dl, respectively. With 24 h after the first dose of ipodate, serum T3 fell by 40%, and it subsequently ranged from 209-278 ng/dl throughout the 39-day ipodate treatment period. Serum T4 also decreased after ipodate administration to 69% and 41% of the pretreatment value after 72 h and 7 days of treatment, respectively; values thereafter during treatment ranged from 19-22 micrograms/dl. These plateau values are in the upper range of normal for the neonatal period. Rapid clinical improvement occurred as the hyperiodothyroninemia abated. Serum rT3 concentrations increased from 468-672 ng/dl to greater than 1400 ng/dl 24 h after each ipodate dose. Thyroid-stimulating immunoglobulin was present in maternal and cord sera, and the half-life of serum thyroid-stimulating immunoglobulin in the infant was approximately 12 days. Antithyroglobulin and antimicrosomal antibodies were present in the infant at 10 days of age, and the titers decreased progressively thereafter; the half-life for the antimicrosomal antibody titer was 3 weeks. The data suggest that sodium ipodate can be useful for treatment of neonatal hyperthyroidism due to Graves' disease.

Antibodies↗
PubMed1987

Molecular cloning and partial characterization of a new autoimmune thyroid disease-related antigen.

To clone and characterize antigens to autoantibodies in Hashimoto's thyroiditis we constructed a cDNA library in the expression vector lambda gt11 using mRNA prepared from Grave's thyroid tissue. This library was screened using serum from a patient with Hashimoto's thyroiditis which had an antimicrosomal antibody titer greater than 1:10(6). Five positive recombinants were identified and cloned. Of these, 3 reacted with 7 of 17 normal serum samples. The 2 other clones (IL-28 and IL-33) reacted with none of the 17 normal serum samples. IL-28 reacted with 4 of 15 and IL-33 with 2 of 15 Hashimoto's thyroiditis serum samples (antimicrosomal antibody titers, greater than 1:6400). The specificity of the interaction between the Hashimoto's thyroiditis samples and the fusion protein was demonstrated by Western blot analysis. In addition, neither 10(-6) M human thyroglobulin nor 100 mU/ml bovine TSH inhibited binding of the serum samples to these 2 clones. Lysate from clones IL-28 and IL-33 did not reduce the antimicrosomal antibody titer in a hemagglutination assay. Absorption of Hashimoto's thyroiditis serum with purified thyroid microsomes reduced the serum antimicrosomal antibody titer, but not binding to these 2 clones. The cDNA inserts of clones IL-28 and IL-33 were approximately 0.6 and 0.4 kilobases (kb), respectively. The 0.6-kb IL-28 insert was used to probe human thyroid and human liver poly(A)+ mRNA. A single band of 3.3 kb was evident only with the thyroid mRNA. The IL-28 insert was subcloned into M13 and sequenced in both directions by the dideoxy technique and found to be 572 basepairs in length. When tested against the GenBank and Dayhoff gene banks, no significant homology with any known sequence was determined. In summary, a cDNA fragment of a previously unrecognized gene coding for an autoimmune thyroid disease-related antigen has been cloned and partly characterized; and the protein produced by this clone is not thyroglobulin, the thyroid microsomal antigen, or the TSH-binding site of the TSH receptor. We have, therefore, identified a new autoimmune thyroid disease-related antigen, the pathogenetic significance of which remains to be determined.

Autoantibodies↗
PubMed1987

Studies on the promoter region of the c-Ha-ras gene in FRTL5 rat thyroid cells.

The functional activity of the promoter region of the rat c-Ha-ras gene was examined in FRTL5 rat thyroid cells, the cell type from which this promoter was cloned. A plasmid (p035-ras-CAT) was constructed containing the untranslated-1 exon as well as 172 base pairs (bp)5' to this exon inserted upstream of the chloramphenicol acetyl transferase (CAT) reporter gene. These 172 bp of 5'-flanking region contain two 10 bp GC box consensus sites and two CAAT boxes. Very weak promoter activity was observed in experiments involving transient transfection of FRTL5 cells with this plasmid, as well as with another plasmid (p5kb-ras-CAT) containing a much more extensive (3.5 kb) 5'-flanking region of the gene. In contrast, strong promoter activity was observed when the same plasmids were transfected into mouse 3T3 fibroblasts. When other promoters (pfos, RSV, and MMTV) were used to drive CAT activity, CAT activity in FRTL5 cells was about 10-fold less than in NIH-3T3 cells and rat embryo fibroblasts. However c-Ha-ras promoter activity was reduced out of proportion in FRTL5 thyroid cells relative to the other cell types (approximately 50-fold less). DNA gel-shift assays performed using crude extracts of FRTL5 and 3T3 nuclear proteins revealed quantitatively similar binding to the same promoter region in the c-Ha-ras 5'-flanking sequence. These data demonstrate that promoter activity of the rat c-Ha-ras gene is contained within the 172 bp 5'-flanking region of the gene. This promoter activity is expressed at a much lower level in slow-growing FRTL5 cells relative to other more rapidly growing cell types.

Animals↗
PubMed1987

Molecular cloning of the complementary deoxyribonucleic acid for human thyroid peroxidase.

Five overlapping cDNA clones representing the entire mRNA for human thyroid peroxidase (TPO) have been isolated from a human Graves' thyroid cDNA library. The cDNA sequence has been determined. Human TPO cDNA contains 3060 bases from the start of transcription to the beginning of the poly (A) tail at the 3'-end. The derived amino acid sequence of human TPO consists of 933 amino acids with a mol wt of 102,937. The derived amino acid sequence contains five potential glycosylation sites (Asn-X-Ser/Thr), a probable transmembrane signal peptide sequence at the amino terminus, and a hydrophobic putative membrane-spanning region beginning 85 amino acid residues from the carboxyl terminal end. Comparison of the human TPO amino acid sequence to that of pig TPO shows strong homology extending from the amino terminus to within 44 amino acid residues of the carboxyl-terminus.

Amino Acid Sequence↗