T4 Ratio Research Articles

Determination of the T1:T2:T3:T4 Ratio in Coordinating Missions of Emergency Physicians (CEP), and Estimate of Mean Severity Index of CEP Missions in Bavaria

Determination of the T1:T2:T3:T4 Ratio in Coordinating Missions of Emergency Physicians (CEP), and Estimate of Mean Severity Index of CEP Missions in Bavaria

Increased Hepatobiliary Clearance of Unconjugated Thyroxine Determines DMP 904-Induced Alterations in Thyroid Hormone Homeostasis in Rats

4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine (DMP 904) is a potent and selective antagonist of corticotropin releasing factor receptor-1 (CRF1 receptor) with an efficacious anxiolytic profile in preclinical animal models. In subchronic toxicity studies in Sprague-Dawley rats, DMP 904 produced thyroid follicular cell hypertrophy and hyperplasia, and a low incidence of follicular cell adenoma. The current investigations were designed to determine the mode of action by which DMP 904 disrupts thyroid homeostasis in male rats. Five-day treatment with DMP 904 (300 mg/kg/day) dramatically lowered serum thyroxine (T4) to levels below detectable limits (< 1 microg/dl) by 72 h, with concurrent decreases in triiodothyronine (T3, about a 70% decrease) and increases in thyroid stimulating hormone (TSH; about a three-fold increase). DMP 904 increased [125I]T4 total body clearance (Cl tb) (38.21 +/- 10.45 ml/h) compared to control (5.61 +/- 0.59 ml/h) and phenobarbital-treated rats (7.92 +/- 1.62 ml/h). This increase in Cl(tb) was associated with a significant increase in biliary clearance (Cl bile) of unconjugated [125I]T4 (nearly 80-times control rates) and increased liver:blood ratios of T4, suggestive of enhanced hepatic uptake of T4. A single dose of DMP 904 (200 mg/kg) increased mRNA levels of hepatic cytochrome P450s (CYP 3A1 and CYP 2B1) and UDP-glucuronosyltransferases (UGT 1A1 and UGT 1A2). DMP 904 also induced mRNAs of the canalicular transporter, multi-drug resistance protein-2 (Mrp2) and sinusoidal transporters, organic anion transporting proteins (Oatp1 and Oatp2) within 24 h. Western blot analysis confirmed DMP 904 related increases in Oatp2 protein expression. Collectively, these data suggest that DMP 904 is an agonist of the constitutive androstane receptor (CAR) and pregnane X receptor (PXR) and that the decreased serum levels of T4 and T3 resulted from increased hepatobiliary clearance. However, DMP 904 is distinguished from other compounds associated with similar effects on thyroid hormone homeostasis because its effects were primarily related to increased biliary excretion of unconjugated T4.

Ratio of Serum Free Triiodothyronine to Free Thyroxine in Graves' Hyperthyroidism and Thyrotoxicosis Caused by Painless Thyroiditis

The serum T3 to T4 ratio is a useful indicator for differentiating destruction-induced thyrotoxicosis from Graves' thyrotoxicosis. However, the usefulness of the serum free T3 (FT3) to free T4 (FT4) ratio is controversial. We therefore systematically evaluated the usefulness of this ratio, based on measurements made using two widely available commercial kits in two hospitals. Eighty-two untreated patients with thyrotoxicosis (48 patients with Graves' disease and 34 patients with painless thyroiditis) were examined in Kuma Hospital, and 218 patients (126 with Graves' disease and 92 with painless thyroiditis) and 66 normal controls were examined in Ito Hospital. The FT3 and FT4 values, as well as the FT3/FT4 ratios, were significantly higher in the patients with Graves' disease than in those with painless thyroiditis in both hospitals, but considerable overlap between the two disorders was observed. Receiver operating characteristic (ROC) curves for the FT3 and FT4 values and the FT3/FT4 ratios of patients with Graves' disease and those with painless thyroiditis seen in both hospitals were prepared, and the area under the curves (AUC), the cut-off points for discriminating Graves' disease from painless thyroiditis, the sensitivity, and the specificity were calculated. AUC and sensitivity of the FT(3)/FT(4) ratio were smaller than those of FT(3) and FT(4) in both hospitals. The patients treated at Ito hospital were then divided into 4 groups according to their FT4 levels (A: < or =2.3, B: >2.3 approximately < or =3.9, C: 3.9 approximately < or =5.4, D: >5.4 ng/dl), and the AUC, cut-off points, sensitivity, and specificity of the FT(3)/FT(4) ratios were calculated. The AUC and sensitivity of each group increased with the FT4 levels (AUC: 57.8%, 72.1%, 91.1%, and 93.4%, respectively; sensitivity: 62.6%, 50.0%, 77.8%, and 97.0%, respectively). The means +/- SE of the FT3/FT4 ratio in the Graves' disease groups were 3.1 +/- 0.22, 3.1 +/- 0.09, 3.2 +/- 0.06, and 3.1 +/- 0.07, respectively, versus 2.9 +/- 0.1, 2.6 +/- 0.07, 2.5 +/- 0.12, and 2.3 +/- 0.15, respectively, in the painless thyroiditis groups. In the painless thyroiditis patients, the difference in the FT3/FT4 ratio between group A and group D was significant (p<0.05). Thus, the FT3/FT4 ratio in patients with Graves' disease likely remains unchanged as the FT4 level rises, whereas this ratio decreases as the FT4 level rises in patients with painless thyroiditis. In conclusion, the FT3/FT4 ratios of patients with painless thyroiditis overlapped with those of patients with Graves' disease. However, this ratio was useful for differentiating between these two disorders when the FT4 values were high.

The Role of Thyroid Hormone in Fish Development with Reference to Aquaculture

Recent progress in an understanding of the role of thyroid hormone (TH) on fish development was reviewed with particular reference to fish farming. TH is a small liposoluble hormone produced in thyroid follicles and has two bioactive forms, tetraiodothyronine (thyroxine, T4) and triiodothyronine (T3). Mother fish deposits a considerable amount of TH in developing oocytes. The amount of TH and ratio of T3 to T4 in eggs vary among species and stocks of the same species. The role of TH in eggs is not yet clear, though enhanced survival and growth of embryos and larvae by the enrichment of the eggs with TH have been reported in some cases. On the other hand, the role of TH that promotes larva-juvenile transition or metamorphosis has been established in teleost fish. The level of TH elevates at the onset of metamorphosis, and the treatment with TH can induce precocious metamorphosis. Considering the TH role in fish development, the disorder of its proper function could lead to deformity in juveniles, which is frequently observed in hatchery. In addition, many environmental chemicals have potential disrupting TH function in developing embryos and juveniles of fish.

Thermal manipulations during broiler chick embryogenesis: effects of timing and temperature

This study aimed at elucidating the effects of thermal manipulation (TM) during different periods of embryogenesis on hatchability, body weight, and thermoregulation of Ross chicks at hatch, and on the chick's ability to cope with thermal challenge (TC) at 3 d of age. Control embryos were incubated at 37.8 degrees C and 56% RH, whereas the TM embryos were treated for 3 h at 39.5 (1) or 41.0 degrees C (2) and 65% RH, during early embryogenesis (EE), E8 to E10, and late embryogenesis (LE) at E16 to E18. At hatch, after feather drying, BW and body temperature (Tb) were measured, blood was drawn from the jugular vein to measure plasma concentrations of thyroxine (T4), triiodothyronine (T3), and corticosterone. These parameters were also measured in 3-d-old chicks during exposure to TC at 41 degrees C for 6 h. Hatchability was significantly higher in the LE1-treated group than in the other treatments. EE1- and LE1-treated embryos exhibited significantly lower Tb at hatch than the LE2 chicks. Significant hyperthermia was noted in the control chicks during 6 h of TC; it coincided with a higher plasma T3 concentration (P = 0.074). During TC, the LE1-treated chicks exhibited the lowest T3 to T4 ratio and a significantly reduced plasma corticosterone concentration. It can be concluded that TM at 39.5 degrees C for 3 h during E16 to E18 of incubation improved chick's thermotolerance acquisition and reduced the corticosterone level of chicks exposed to TC at the age of 3 d.

Low-temperature arrest of the triiodothyronine-dependent transcription in Rana catesbeiana red blood cells.

We examined possible molecular mechanisms for the low-temperature arrest of T3-induced Rana catesbeiana metamorphosis. Scatchard plots revealed that the ratios of maximum binding capacity/dissociation constant for high-affinity sites of tadpole serum proteins for T3 at 20 and 28 C was 3.3-4.6 times less than that at 4 C, due to the decrease in maximum binding capacity values. Kinetic studies of T3 uptake into tadpole red blood cells demonstrated that the ratio of maximum uptake rate/Michaelis constant at 23 C was approximately 13 times greater than that at 4 C. The process of intracellular transport of T3 into the nucleus was not arrested at 4 C. The ratio of T3 incorporated into nuclei to that taken up into red blood cells was not significantly different at 4, 20, and 28 C, indicating the absence of temperature-sensitive sites in this process. T3 binding to the T3 receptors alpha and beta were not temperature sensitive at least at 4 and 20 C. Transcription of the tr genes, early primary T3 response genes, was activated by 10 nM T3 at 20 and 28 C but was barely detected at 4 C. These results indicate that the major molecular event causing the low-temperature arrest of amphibian metamorphosis occurs after T3 entry into the nucleus but before or during the transcriptional activation of the tr genes. Plasma proteins binding T3 and the cellular thyroid hormone uptake system on the plasma membrane may contribute to the slowing of the incorporation of T3 into nucleus at 4 C by decreasing the uptake velocity of T3.

Relationships between PCBs and thyroid hormones and retinol in female and male polar bears.

We studied the relationships between polychlorinated biphenyls (PCBs) and thyroid hormones (THs) and retinol within two groups of female polar bears (Ursus maritimus), females with cubs of the year (FWCOY) and females without cubs of the year (FWOCOY), and within a group of males. Concentrations of five of the six quantified PCB congeners, i.e., PCB-99, PCB-153, PCB-156, PCB-180, PCB-194 (sigma PCB5), correlated with each other, whereas the concentrations of PCB-118 did not correlate with the other congeners. sigma PCB5 and PCB-118 did not differ between the three different groups of polar bears, and the plasma levels ranged from 16.7 to 203.2 ng/g wet weight (ww) for sigma PCB5 and from 0.09 to 0.93 ng/g ww for PCB-118. PCBs did not affect the retinol status in any of the three groups. In FWCOY, we found negative correlations between sigma PCB5 and the three TH variables free thyroxin (FT4) (r2 = 0.35), free triiodothyronine (FT3) (r2 = 0.30), and the total T4:total T3 ratio (TT4:TT3) (r2 = 0.92). In FWOCOY, sigma PCB5 was negatively correlated to TT4 (r2 = 0.14) and positively correlated to TT3:FT3 (r2 = 0.31), whereas PCB-118 was positively correlated to FT3 (r2 = 0.21) and negatively correlated to TT3:FT3 (r2 = 0.26). In males, sigma PCB5 was negatively correlated to FT3 (r2 = 0.56) and positively correlated to FT4:FT3 (r2 = 0.78), whereas PCB-118 was negatively correlated to FT4:FT3 (r2 = 0.53). Thus, PCBs affected five TH variables in the female polar bears (TT4, FT4, FT3, TT3:FT3, TT4:TT3), but PCBs affected only two TH variables in males (FT3, FT4:FT3). Female polar bears could be more susceptible to TH-related effects of PCBs than are males. PCBs also affected T3 to a larger degree than T4.

Epigenetic and gene expression changes related to transgenerational carcinogenesis.

Transgenerational carcinogenesis refers to transmission of cancer risk to the untreated progeny of parents exposed to carcinogens before mating. Accumulated evidence suggests that the mechanism of this process is epigenetic, and might involve hormonal and gene expression changes in offspring. To begin to test this hypothesis, we utilized a mouse model (NIH Swiss) in which exposure of fathers to Cr(III) chloride 2 wk before mating can alter incidence of neoplastic and nonneoplastic changes in offspring tissues. Utilizing a MS-RDA approach, we found that the sperm of these fathers had a significantly higher percentage of undermethylated copies of the 45S ribosomal RNA gene (rRNA); this finding was confirmed by bisulfite sequencing. Because gene methylation is a known mechanism of expression control in germ cells, and ribosomal RNA levels have been linked to cancer, these findings are consistent with the hypothesis. Secondly, we observed that offspring of Cr(III)-treated fathers were significantly heavier than controls, and had higher levels of serum T3. Possible effects of T3 levels on gene expression in the offspring were examined by microarray analysis of cDNAs from liver. A total of 58 genes, including 25 named genes, had expression ratios that correlated significantly with serum T3 ratios at P </= 0.001. Some of these genes have potential roles in growth and/or tumor suppression. These results also support the hypothesis of an epigenetic and/or gene expression-based mechanism for transgenerational carcinogenesis. Published 2004 Wiley-Liss, Inc.

Effects of organochlorine contaminants on thyroid hormone levels in Arctic breeding glaucous gulls, Larus hyperboreus.

Studies on glaucous gulls (Larus hyperboreus) breeding in the Barents Sea have reported that high blood levels of halogenated organic contaminants in this species might cause reproductive, behavioral, and developmental stress. However, potential endocrine system modulation caused by contaminant exposure has yet not been reported in this Arctic apical predator. In this present study we aimed to investigate whether the current levels of a selection of organochlorines (OCs) were associated with altered circulating levels of thyroid hormones (THs) in free-ranging adult glaucous gulls breeding at Bear Island in the Barents Sea. Blood concentrations of 14 polychlorinated biphenyls, hexachlorobenzene (HCB), oxychlordane, and p,p' -dichlorodiphenyldichloroethylene (p,p' -DDE) were quantified, in addition to free and total thyroxine (T4) and triiodothyronine (T3), in plasma of 66 glaucous gulls in the spring of 2001. Negative correlations were found between plasma levels of T4 and T4:T3 ratio, and blood levels of OCs in male glaucous gulls. Despite their relatively low contribution to the total OC fraction, HCB and oxychlordane were the most prominent compounds in terms of their negative effect on the variation of the T4:T3 ratio. Moreover, lower T4 levels and T4:T3 ratios were measured in glaucous gulls breeding in a colony exposed to high levels of OCs, compared with a less exposed colony. Levels of T3 were elevated in the high-OC-exposed colony. This may indicate that the glaucous gull is susceptible to changes to TH homeostasis mediated by exposure to halogenated organic contaminants.

Nonthyroidal illness syndrome in patients with subarachnoid hemorrhage due to intracranial aneurysm.

We have previously reported that subarachnoid hemorrhage due to ruptured intracranial aneurysm (SH) is associated with changes in the hormonal profile in the first 24 hours after the event. We proposed that the hormonal changes observed are due to the intense stress to which the patients are exposed. However, the thyroidal hormonal profile is indicative of the presence of a nonthyroidal illness syndrome (NTIS). In this paper, we examined whether the change in the thyroid hormone profile is compatible with a NTIS. Two groups of patients were included in the study: A) 30 patients with SH (21 females and 9 males; 41.7+/-11.4 years) and B) a control group including 25 patients with benign diseases of the spine (BDS) (lumbar disc hernia or stable spinal trauma) (8 females and 17 males; 41.3+/-14.2 years). In a subgroup of eight patients of each group serum triiodothyronine (T3) and reverse T3 levels were measured. The blood samples were obtained between 8:00 and 9:00 AM. The following results were obtained: The SH group had smaller serum T3 and free T4 levels than the BDS group (p<0.05): T3 (ng/mL): SH = 58.7+/-1.1 and BDS = 74.5+/-13.9; free T4 (ng/dL): SH = 0.9+/-0.2 and BDS = 1.1+/-0.3. There was no significant difference in the serum levels of total thyroxine (T4) and thyroid-stimulating hormone (TSH) between the two groups: T4 ( microg/dL): SH = 6.9+/-1.1 and BDS = 7.4+/-2.1; TSH ( microUI/mL): SH = 1.5+/-0.8 and BDS = 1.8+/-1,0. In the sample of eight patients of each group we had the following results: T3 (ng/mL): SH = 66.8+/-3.8 and BDS = 77.2+/-1.1 (p <0.05); reverse T3 (ng/dL): SH = 32.8+/-8 and BDS = 24.7+/-2.2 (NS); T3/ reverse T3 ratio: SH = 2.6+/-0.3 and BDS = 3.3+/-0.4 (NS). Thyreoglobulin and microsomal antibodies were not detectable, except in one patient in the SH group. In conclusion, the SH patients present serum levels of T3 and free T4 significantly lower than that of BDS patients; the thyroidal hormone profile suggests that SH patients have developed the nonthyroidal illness syndrome.

Thyroid status is related to migratory behavior in Anguilla anguilla glass eels

To determine whether thyroidal status is related to migratory and settling behavior in Anguilla anguilla glass eels, we sampled glass eels showing different migratory behaviors in the Arzal dam, which constitutes the tidal limit of the Vilaine River (France). We collected 4 groups of glass eels: flood and ebb tide glass eels were netted in the estuary during the flood and ebb tides, respectively, trap glass eels were sampled from the eel ladder trap, and bottom glass eels sheltering on the bottom of the estuary during flood tide. We measured individual whole-body triiodothyronine (T3) and thyroxine (T4) levels for these groups, and calculated total thyroid hormone (TH) levels as T3 + T4 contents reflecting the thyroid gland secretory activity, and T3:T4 ratios reflecting T4 outer-ring desiodase (T4 ORD) activity. Trap glass eels had the highest TH levels, indicating an activation of the thyroid gland via the thyreotrop axis. This could be responsible for the behavioral transition (loss of circatidal rhythm and switch to counter-current swimming) at the tidal limit and active colonization of river habitats by glass eels. Ebb and flood tide glass eels had similar TH levels that were lower than those of trap glass eels, indicating a lower thyroid gland secretory activity in the former. Ebb tide glass eels had higher T3:T4 ratios than flood tide and trap glass eels, indicating physiological stress related to inefficient use of tidal streams. Bottom glass eels had the lowest TH levels, and high T3:T4 ratios similar to those of ebb tide glass eels; this suggests that physiological stress induced by fre- quent counter-current swimming leads to precocious settlement of glass eels in estuarine habitats. Our data supports the critical role of the thyroid status in the migratory and settling behavior of glass eels in estuarine and marine habitats.

Selenium and iodine status relationship in calves and heifers from selenium and iodine deficient areas in Serbia

The selenium and iodine status was determined in calves (3, 6 and 9 months old) and heifers (12 months) on two farms (A-Kovin, and B-Vrbas) in iodine and selenium deficient areas of Serbia. Selenium concentrations in feedstuffs on the territories surrounding farm A and B were lower than 0.1 ppm in more than 90% of the samples and lower than 0.05 ppm in more than 67% of the samples. Plasma selenium concentrations in calves and heifers from both farms were very low, ranging from 1.58 to 9.42 µg/L. Plasma GSH-Px activity was very low in 3 month old calves: 8.4 ± 5.2 and 16.1 ± 4.3 µkat/L on farm A and B, respectively, and significantly higher in 12 month old heifers: 39.0 ± 6.2 and 40.8 ± 9.8 µkat/L on farm A and B, respectively. Mean plasma T4 levels in all groups of calves and heifers were relatively high, ranging between 57.1 and 102.9 nmol/L. Mean plasma T3 levels in calves and heifers from both farms ranged from 2.72 to 3.51 nmol/L, and did not vary significantly, except for the 3-month-old calves on farm B, where the level was significantly higher than in the other groups. A significant correlation was found between plasma GSH-Px activity and T3:T4 ratio in the 6- month-old calves from farm A (r2 = 0.80), as well as in the combined groups of 6-and 9-month old calves from farm B (r2 = 0.68).

Rare Thyrotoxicosis Develops in Patient with Lung Cancer Metastasis to Thyroid

Rare Thyrotoxicosis Develops in Patient with Lung Cancer Metastasis to Thyroid

Nonrandom intragenic variations in patterns of codon bias implicate a sequential interplay between transitional genetic drift and functional amino acid selection.

Although most codon third bases appear to be functionless, the synonymous codons so defined exhibit a strikingly nonrandom distribution (codon bias) within human and other genes. To examine this phenomenon further, we generated a database of DNA sequences encoding human transmembrane cell-surface receptor proteins. Using this database we show here that the guanine and cytosine content of codon third bases (GC3) varies intragenically with the nature of the specified receptor domains (transmembrane > extracellular > intracellular domains; p < 0.001), the phenotype of the encoded amino acids (hydrophobic > hydrophilic > neutral amino acids; p < 0.001), and the receptor affiliation of the transmembrane (G-protein-coupled receptors > receptor tyrosine kinases; p < 0.001). Within gene regions specifying transmembrane domains, GC3 declines as domain functionality becomes redundant with increasing hydrophobicity (p < 0.001). Codons containing the second-base cytosine (XCZ, which encodes neutral amino acids) are selectively depleted of third-base adenine content (A3: XCA codons) when encoding transmembrane domain residues, consistent with positive selection for transitional mutation of XCG to XTG (which encodes hydrophobic amino acids) rather than to the synonymous XCA. Supporting this XCG --> XTG mechanism of codon bias, the G3:A3 ratio of codons specifying the transmembrane amino acid glycine (GGZ) is intermediate between that of its functional homolog alanine (GCZ) and that of hydrophobic valine (GTZ), even though the C3:T3 ratios are similar. Conversely, nearest-neighbor analysis of third bases 5' to codons specifying valine and leucine (CTZ) confirms a significant difference in C3:T3 but not G3:A3 ratios (i.e., C3/G1 --> T3/G1 > C3/A1; p < 0.001), consistent with the functionally advantageous retention of hydrophobic residues. These data raise the possibility that patterns of intragenic codon bias reflect a balance between negative and positive selection, suggesting in turn that analysis of codon third-base usage may help to predict the functional significance of encoded products.

Environmental Incubation Factors Influence Embryonic Thyroid Hormones

Thyroid hormone responses in embryonic avian species are of two types, developmental and metabolic. Many studies have characterized the developmental function of the turkey embryonic thyroid, but few have characterized the metabolic function. Therefore, the purpose of this study was to describe the response of turkey embryonic thyroid hormones to three environmental factors. We proposed that embryonic thyroids from different genetic backgrounds would respond differently to changes in maternal diet and incubation temperature.Lines of turkeys known to have different embryonic growth and survival were examined in the current study. These eggs differ in egg weight, eggshell conductance, hatchling weight and organ maturity at the time of hatching. Eggs were produced throughout a 20 wk laying period and embryos were sampled at monthly intervals. Half of the hens producing the eggs were fed additional iodide in their diets, then, subsequently, half of each dietary treatment and line combination were incubated at either 36.8 C or 37.5 C to prolong the incubation period. Embryos were sampled during the final week of incubation when thyroid hormones become elevated to effect maturation and survival functions in turkey embryos. Embryonic thyroxine (T4) and triiodothyronine (T3) levels were assayed by RIA and compared among the treatments. Line, diet, and incubation period interacted to affect the levels of T4, T3 and T3 to T4 ratios in the turkey embryonic during late incubation. It was concluded that environmental factors can affect circulating thyroid hormone levels in turkey embryos, thus affecting metabolic functions, and the possibility exists to manipulate these circulating levels using environmental incubation conditions to improve hatchability.

Levothyroxine therapy and serum free thyroxine and free triiodothyronine concentrations.

Although the normal thyroid gland secretes both levothyroxine (L-T4) and levotriiodothyronine (L-T3), normalization of serum TSH with L-T4-replacement therapy alone in hypothyroidism is generally believed to result in a normal serum L-T3 and to reflect a euthyroid state. However several recent studies suggest that this may not be the case. Accordingly, the relationship between serum free L-T4 and free L-T3 was examined in 20 normal individuals (group A) and in 53 patients with chronic autoimmune thyroiditis, 18 with normal TSH on no L-T4-replacement (group B), and 35 with normal TSH on L-T4-replacement therapy for hypothyroidism (group C). Data were analyzed by applying a one-way analysis of variance with correction for multiple comparisons. Serum TSH values were very similar among the 3 groups. In groups A and B, mean serum free T4 and free T3 were very similar. In group C, the mean free T4 (16+/-2 pmol/l) was significantly higher than the values in groups A (14+/-1) and B (14+/-2) (p<0.001) and the mean free T3 lower (4.0+/-0.5 pmol/l vs 4.2+/-0.5, NS and 4.4+/-0.5, p<0.02). Consequently, the mean molar ratio of free T4 to free T3 was significantly higher in group C than the ratios in groups A and B (p<0.0001), despite very similar TSH values. These findings indicate that in hypothyroid patients L-T4-replacement, that is sufficient to maintain a normal serum TSH, is accompanied by a serum free T4 that is higher than that in untreated euthyroid patients or normal individuals and may not result in an appropriately normal serum free T3 concentration.

Thyroid of Lake Sturgeon, Acipenser fulvescens: I. Hormone Levels in Blood and Tissues

The authors measured thyroid hormone (TH) levels in plasma, whole carcass, and tissues of cultured 2-year-old immature lake sturgeon held in fresh water and in serum of adults at spawning time from the Winnipeg River. Circulating thyroxine (T4) and 3,5,3′-triiodothyronine (T3) levels were low (T4 ∼ 0.3 ng/ml, T3 ∼ 0.2 ng/ml) in all cultured fish and most adults, but a few of the latter had exceptionally high T4 and T3 levels. The percentages of blood TH found in erythrocytes were 19.5% (T4), 6.1% (T3) and 6.9% (reverse T3 = rT3). Equilibrium dialysis showed much higher percentages of plasma free (F) FT4 (1.1%), FT3 (0.4%), and FrT3 (3,3′,5′-triiodothyronine = rT3, 3.0%) for sturgeon than for rainbow trout, indicating more limited TH binding to sturgeon plasma sites. However, concentrations of FT4 and FT3 were close to those reported for salmonids. T3 levels exceeded T4 levels in most extrathyroidal tissues of cultured sturgeon but in most cases were less than 0.1 ng/g and 10 to 100 times lower than reported for salmonids; only the whole brain T3 concentration (5.6 ng/g) approached that of salmonids. The digested thyroid contained 21.3 ng T3/g and 2.4 ng T4/g. The authors conclude that lake sturgeon have a low circulating reserve of bound TH but have FT4 and FT3 concentrations close to those of salmonids. The high thyroidal T3:T4 ratio and low tissue T4 levels suggest that, in contrast to teleosts studied to date, the thyroid may be a significant direct source of T3, the primary TH in sturgeon tissues. High serum T4 and T3 levels in some sturgeon at spawning time may suggest a thyroid role in reproduction.

Effects of ubenimex (bestatin) on the immunity of patients with squamous cell lung carcinoma treated with chemotherapy

To evaluated the effects of ubenimex on immunity of patients with squamous cell lung cancer. Fifty-six patients with inoperable squamous cell lung carcinoma were randomly divided into the experimental group ( EG, received chemotherapy combined with ubenimex 30mg p. o. daily for 6 months) or the control group ( CG, received chemotherapy alone) at 3:2 ratio. Lymph ocyte counting ( LC) , OKT₄ /T₈ ratio, activity of NK cell, IL-2 value and the level of soluble interleukin-2 receptor were determined. The regimen was CAP: cyclophosphamide and adriamycin and cisplatin. Fifty-two patients were evaluable to be analysed and 32 in the EG and 20 in the CG respectively. The overall response rate at 6 months after treatment was 56% ( 18/ 32) in the EG and 45% ( 9/ 20) in the CG, which was no significant difference between the two groups. Three months and 6 months after treatment, OKT₄ /T₈ ratio, activity of NK cell and IL-2 value of the patients in the EG were significantly increased with the values of 1. 50±0. 29 and 1. 63±0. 39, 35. 1%±7. 3% and 35. 8%±5. 0%, 12±2 IU/ ml and 13±3 IU/ ml respectively compared with those before treatment with the values of 1. 34±0. 32, 33. 6%±5. 5%, 11±2 IU/ ml respectively ( P < 0. 05) and the SIL-2R level was significantly decreased with the values of 596±140 IU/ ml and 581±138 IU/ ml respectively compared with those before treatment 660±173 IU/ ml ( P < 0. 05) . Whereas in the CG there were no significant changes observed except for the SIL-2R level with the value of 532±78 IU/ ml at 6 months after treatment vs 645±189 IU/ ml before treatment. The IL-2 level of the patients in the EG significantly increased compared with those in the CG ( P < 0. 05) at 6 months after treatment ( 13±3 IU/ ml vs 11±3 IU/ ml) . Ubenimex may increase the OKT₄ / T₈ ratio, the NK cell activity and the IL-2 value and decrease the SIL-2R level of patients with squamous cell lung carcinoma. Further studies on larger cases and long period of follow-up will be needed before definite conclusion can be drawn.

Influence of type II 5' deiodinase on TSH content in diabetic rats.

The influence of hypothalamic and pituitary type II 5'deiodinase (5'D-II) activities and T3 content on pituitary TSH content was investigated in streptozotocin (STZ)-induced diabetic rats (D). The results show, first, that hypothalamic and pituitary 5'D-II activities were lower in neonatal D rats versus control (C) rats, and the normal developmental pattern was altered. Secondly, when D and C rats were thyroidectomized (Tx) at 25 days of age (D+Tx, C+Tx), pituitary and hypothalamic 5'D-II activities increased ten days later in both populations vs. intact rats, but the percentage of increase was smaller in D+Tx than in C+Tx. The hypothalamic T3 to T4 ratios were also decreased in D+Tx animals (0.38) as compared to C+Tx rats (1.64). The hypothalamic T3 content was reduced by 30% in D as compared to C rats and by 80% in D+Tx as compared to C+Tx rats, showing a defect in hypothalamic T4 deiodination. Pituitary TSH content increased after Tx in D+Tx, but not in C+Tx. These results in diabetic rats indicate that the hypothalamic and pituitary 5'D-II activity and hypothalamic T3 content are affected by diabetes and play a role in the regulation of pituitary TSH content.

Entry of thyroid hormones into tilapia oocytes

The patterns of entry of thyroid hormones into live tilapia oocytes were examined by incubating ovarian follicles in L-15 medium containing 125I-labeled thyroxine (T4) or 3,5,3′-triiodothyronine (T3). As judged from HPLC profiles, radioactivity in extracts of follicles immersed in T3 was identified to reside in T3, while most of the radioactivity in the extract of T4 immersed follicle was not associated with T4. Radioactivity of T3 immersed follicles reached a constant level after 18 h of incubation. Entry of T3 into the oocytes was non-saturable within the range of 0.5–5000 ng/ml of T3 in the incubation medium, suggesting the absence of specific mechanisms for T3 entry into the oocyte. Presence of female plasma at a level of 20% of incubation medium inhibited the T3 entry into the oocytes by approximately 80%. When follicles were back-transferred to medium without T3, only 15% of T3 in the oocyte disappeared within the following 24 h. From our results, we conclude that free T3 seems to enter oocytes freely across the membranes by diffusion, and that T3 in the oocytes may bind to some molecules in the oocyte. However, during egg formation in vivo, contribution of free T3 entry into the oocytes did not seem to be significant when considering the free T3 ratio in female plasma.