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We measured serum and urinary 1,5-anhydro-D-glucitol (1,5-AG) during a glucose tolerance test (GTT) in patients with chronic renal failure (CRF) and compared the fractional excretion of 1,5-AG (FEAG) with that of diabetes mellitus (DM) patients and healthy controls. The mean serum 1,5-AG in CRF patients [60 ± 23(SE) μmol/L] was significantly lower than in controls (155 ± 7 μmol/L) in spite of a normal glycaemia. The levels in the CRF group were similar to those in the DM group. During GTT, the blood glucose profile in the CRF group was not significantly different from that of the control group, and urinary glucose excretion was negligible. However, FEAG was significantly higher in CRF patients than in controls. These data suggest that serum 1,5-AG in patients with CRF decreases due to a decrease in 1,5-AG reabsorption, independently of glucose excretion, and that serum and/or urinary 1,5-AG can be a useful marker for renal tubular dysfunction because the 1,5-AG reabsorption system is more vulnerable than the glucose reabsorption system.

We investigated the effects of streptozotocin (STZ)-induced diabetes on thyroid hormone levels, type 1 deiodinase (D1) activity and messenger RNA (mRNA) levels in inherited D1 deficient C3H mice in a comparative manner with control C57 mice. The apparent maximum velocity (Vmax) D1 values in C3H mice were 3% (liver) and 26% (kidney) of those in C57 mice. In C3H mice, similar serum T3, slightly higher T4, and 2.6-fold higher rT3 levels were observed compared with C57 mice. In STZ-induced diabetes, serum T4 level markedly decreased in both C3H and C57 mice. Serum T3 levels in STZ-C3H mice similarly decreased as in STZ-C57 mice. On the other hand, serum rT3 levels increased to 3.3-fold higher in STZ-C3H than in STZ-C57 mice. The Vmax values were decreased to 12% (STZ-C3H) and to 30% (STZ-C57) in liver, and decreased to 33% (both STZ-C3H and STZ-C57) in kidney. The changes in D1 mRNA levels in diabetes versus control were comparable to those of D1 activities in both strains. In summary, similar mechanism(s) to those which decrease the D1 expression and the serum T3 level in diabetes, function in D1 deficient C3H mice as in C57 mice. It appears that hepatic and renal D1 activity alone can not explain the similar reduction in T3 level in STZ-C3H mice and STZ-C57 mice.

We previously demonstrated that iodothyronine 5'-deiodination (5'D) activity is present and increased by triiodothyronine (T3) and angiotensin II (Ang II) in cultured rat cardiac myocytes. To further elucidate the stimulatory mechanism of Ang II, we investigated the effect of intracellular Ca2+ and protein kinase C on myocardial 5'D activity. Moreover, to elucidate the molecular mechanism of the stimulatory effect of T3 and Ang II, we detected the mRNA levels by means of a reverse-transcriptase polymerase chain reaction (RT-PCR). 5'D activity was increased by adding Bay-k 8644, Ca2+ channel agonist and the effect of Bay-k 8644 was completely blocked by nifedipine, a Ca2+ channel antagonist. 12-O-tetradecanoylphorbol-13-acetate, a protein kinase C activator, similarly stimulated 5'D activity. The addition of a high concentration (20-40 mM) of K+, which caused the depolarization of the membrane had significant stimulatory effects on 5'D activity. Type 1 deiodinase (D1) mRNA was evident in myocardial cells by RT-PCR in a single 758 bp band similar to that in the liver. Cardiac fibroblasts did not express the D1 mRNA. A significant increase in D1 mRNA was also evident after adding T3 and Ang II. These findings indicate that 5'D activity in myocardial cells is increased by activating the voltage sensitive Ca2+ channel, protein kinase C, and membrane depolarization, and that the D1 mRNA is present in cardiac myocytes and is increased by T3 and Ang II. This study therefore suggests that Ang II could affect the action of thyroid hormone on the heart by increasing the D1 gene expression.

To examine the mechanism behind a decrease in type 1 iodothyronine deiodinase (D1) gene expression in diabetes mellitus, we evaluated the effect of administering T3 and/or insulin on D1 activity and the mRNA levels in the liver of streptozotocin (STZ)-induced diabetic rats. STZ (100 mg/kg BW) was administered to male Wistar rats, and the rats were divided into four groups as follows: (1) STZ alone, (2) STZ and T3 (5 microg/100 g BW daily for 7 days), (3) STZ and insulin (intermediate-acting insulin, 4 units/100 g BW daily for 7 days), and (4) STZ, T3, and insulin. Blood glucose levels increased in Group 1, but were normalized in Group 3. Serum T3 levels were markedly decreased in Group 1. They were within normal limits 24 hours after the last administration of T3 in Group 2 and after the administration of insulin in Group 3. T3 levels were supranormal in Group 4. TSH levels were normal in Groups 1 and 3, but were suppressed in Groups 2 and 4, suggesting that rats in Groups 2 and 4 were actually in a hyperthyroid state after injecting a large amount of T3. D1 activity in Group 1 was reduced significantly, but it was normal in Groups 2 and 3, and increased in Group 4. D1 mRNA levels in the liver in Group 1 decreased significantly, but they were increased to within normal limits by adding insulin in Group 3. They were also normal in Group 2 where hyperglycemia was evident and rats were hyperthyroid after administering T3. D1 mRNA in Group 4 increased significantly where glucose levels were normal and T3 levels were increased. We suggest that the decrease in hepatic D1 mRNA in STZ-induced diabetic rats is due to metabolic derangement caused by insulin deficiency in addition to a possible decrease in tissue T3 availability.

The present study was undertaken to evaluate thyroid function and thyrotropic action of hCG in multiple pregnancy. We examined serum samples from 9 multiple pregnant women (3 triplets and 6 twins) and 27 singleton pregnant women as control subjects. Serum hCG levels in multiple pregnancy were higher than those in singleton pregnancy in the second and third trimesters (P < 0.01). The mean free T3 and T4 concentrations in multiple pregnancy did not differ from those in singleton pregnancy in each trimester. Serum hCG levels showed a statistically significant positive correlation with free T3 and T4 levels in singleton pregnancy (P < 0.001). However, these correlations were not observed in multiple pregnancy. Thyroid stimulation activity (TSA) determined by cAMP accumulation in FRTL-5 cells in multiple pregnancy sera was significantly higher than that in singleton pregnancy in the first trimester (P < 0.05), but did not differ in the second and third trimesters. Moreover, TSA did not show any correlation with serum hCG levels in multiple pregnancy in contrast with the results in normal pregnancy. A bioactivity/immunoreactivity ratio of hCG in multiple pregnancy was lower than in singleton pregnancy in the second and third trimesters. The discrepancy between immunoreactivity and thyrotropic activity of hCG may be caused by the variable thyrotropic potency of heterogeneous hCG molecules in multiple pregnancy.

To evaluate the regulatory mechanism of human Type 1 iodothyronine deiodinase (D1) gene expression, we measured the D1 mRNA levels in peripheral blood mononuclear cells (PBMC) in normal control subjects and in patients with Graves' disease. We used competitive reverse transcriptase-polymerase chain reaction with the deleted complimentary RNA of D1 as the standard for quantification. The D1 mRNA levels in PBMC were increased significantly in patients with Graves' disease compared with that in normal controls. There was a significant (p < 0.01) positive correlation (r=0.698) between D1 mRNA level and serum T3 concentration. When PBMC from the normal volunteers were cultured with various doses of T3, the quantity of D1 mRNA increased significantly in a dose-dependent manner. These findings indicate that PBMC D1 mRNA is actually up-regulated by T3in vivo,and we postulate that a vicious spiral of increasing T3 and D1 is responsible for the exacerbation of thyrotoxicosis in hyperthyroid Graves' disease.

Some occult thyroid carcinomas are hypothesized to regress and be eventually obliterated. We report here a patient whose condition supports this hypothesis. A 51-year-old male with primary hypothyroidism due to Hashimoto's thyroiditis suffered from a rib bone tumor. He had a diffuse goiter with no nodular lesion. Serum FT4 and TSH concentrations were 0.8 ng/dl and 36.4 microU/ml on taking 100 microg/day of T4. Anti-Tg- and -TPO-Ab were strongly positive (99 and 1380 U/ml). The iodine 123 scintigraphy demonstrated clear accumulation in the rib tumor, whereas the thyroid was scarcely visible. Biopsy of the rib tumor showed papillary proliferation of large atypical cells, which were immunohistochemically positive for thyroglobulin. Metastatic bone tumor of papillary thyroid carcinoma was therefore strongly suspected. He underwent a total thyroidectomy and the thyroid was stepwise sectioned completely at 3 mm intervals. The thyroid condition was diagnosed as Hashimoto's thyroiditis demonstrating diffuse and dense fibrosis, lymphocyte infiltration with lymphoid follicles and flattened atrophied follicles, but no carcinomatous foci were found. He was treated with I-131 and scintigraphy after the ingestion showed distinct accumulation in the rib tumors similar to that before thyroidectomy. No other abnormal uptake was observed. It is suggested that the primary occult thyroid papillary carcinoma regressed and was obliterated possibly by some immunologic or other host-resistance factors after it metastasized to the distant bone.

We report a 62-year-old male patient who had variant angina and isolated adrenocorticotropic hormone(ACTH) deficiency. His serum sodium concentration was low and vasopressin was inappropriately high for the low plasma osmolality. Serum free thyroxine (FT4) was low and thyroid stimulating hormone (TSH) was high with positive anti-thyroperoxidase antibodies, compatible with Hashimoto's thyroiditis. Treatment with Amrodipine and hydrocortisone relieved chest symptoms and hyponatremia, and hypothyroidism was also normalized. It is suggested that coronary artery spasm may be related to cortisol deficiency and/or inappropriately high vasopressin secretion and that hypothyroidism was ameliorated because the reduced responsiveness to TSH returned to normal due to hydrocortisone supplement.(Internal Medicine 37: 398-402, 1998)

A 44-year-old woman developed hyperthyroidism due to the coexistence of Graves' disease and an autonomously functioning thyroid nodule (AFTN). Anti-thyrotropin receptor antibody (TRAb) was strongly positive (83.2%), and a thyroid scan initially showed diffuse uptake of Tc-99m pertechnatate in both lobes and further increased uptake in accordance with the right lobe nodule. The nodule in the right lobe was histologically diagnosed as thyroid follicular adenoma. After she was maintained in a euthyroid state by treatment with Methymazole (MMI), thyroid uptake of Tc-99m in the nodule became lower and was slightly suppressed by T3 administrations probably due to its dependence on TSH. Subtotal thyroidectomy was performed and she subsequently became euthyroid with negative TBII activity. It is concluded that she had a coexisting functioning nodule with Graves' disease (Marine-Lenhart syndrome) and that the nodule changed from hot to cool along with the anti-thyroid treatment, unlike usual cases of this syndrome showing a cold nodule on the initial imaging under the hyperthyroid state. Repeated Tc-99m pertechnatate thyroid scans were helpful in evaluating the reaction of MMI and TSH in both lesions separately in the present case.

To evaluate the relationship between eye changes and autoantibody to the thyrotropin receptor in patients with Graves' disease, we evaluated the eye changes using magnetic resonance imaging and the results were correlated with thyroid-stimulating antibody, thyrotropin binding inhibitor immunoglobulin and thyroid growth activity. Subjects were 15 patients with Graves' disease who had Graves' ophthalmopathy, including exophthalmos and other signs and symptoms, and nine patients without ophthalmopathy; all were maintained in a euthyroid state by antithyroid drugs. The thyrotropin-binding inhibitor imunoglobulin was measured by a kit, and thyroid-stimulating antibody and thyroid growth activity were evaluated by cyclic adenosine 3′,5′-monophosphate production and [3H]thymidine incorporation, respectively, by cultured functional rat thyroid lined cells. The sum of the swelling ratios (muscle thickness to the diameter of the optic nerve) of the four extraocular muscles correlated well with the degree of exophthalmos. The thyrotropin-binding inhibitor immunoglobulin was positive in nine out of 15 patients with ophthalmopathy; however, no correlation was observed between the activity and exophthalmos or muscle swelling. No significant correlation was observed between muscle changes and thyroid growth activity either. On the other hand, thyroid-stimulating antibody (642±91%) in Graves' patients with ophthalmopathy was significantly (p

We investigated the regulation of type I iodothyronine 5'-deiodinase (5'-D) gene expression by TSH and T3 in FRTL-5 rat thyroid cells. Northern blot analysis revealed that these cells express a 5'-D messenger RNA (mRNA) species of 2.1 kilobases. Readdition of TSH to FRTL-5 cells, precultured in both thyroid hormones and TSH-depleted medium for 4 days, increased 5'-D mRNA levels, reaching a maximum (2.8-fold compared to control) after 12 h of TSH (10 microU/ml) stimulation. Dibutyryl cAMP (DBC) and forskolin mimicked this stimulatory effect of TSH on 5'-D mRNA levels. T3 also increased the 5'-D mRNA levels, reaching a maximum (2-fold compared to control) after 8 h of T3 (10(-9) M) stimulation. Addition of TSH (10 microU/ml) or DBC (1 mM) together with T3 (10(-9) M) further increased 5'-D mRNA levels, reaching a maximum (5-fold compared to control) after 12 h of stimulation. Examination of the rate of disappearance of 5'-D mRNA levels after inhibition of mRNA transcription by actinomycin-D revealed that neither TSH nor T3 significantly affected the rate of disappearance. Cycloheximide, a protein synthesis inhibitor, almost completely blocked the induction of 5'-D mRNA by TSH and DBC, but did not block the induction by T3. These results suggest that both TSH and T3 increase 5'-D mRNA levels probably by increasing transcription rate, and that TSH regulates it, in part via the second messenger cAMP, for which cycloheximide-sensitive de novo protein synthesis is required, whereas T3 does without requiring it.

A 30-year-old Japanese female developed insulin-dependent diabetes mellitus (IDDM). She later complained of muscle pains at the age of 37. Erythrocyte sedimentation rate and C-reactive protein were abnormal, with negative antinuclear antibody and rheumatoid factor tests. The diagnosis of polymyalgia rheumatica (PMR) was made. She had HLA phenotypes including A2 and without DR4, consistent with common types of Japanese PMR. Her DNA typing included DQB1*0303 which is positively associated with Japanese IDDM. It seems likely that she suffered from these diseases at a young age on the basis of having the HLA-susceptibility to both PMR and IDDM.

A-65-year-old man was admitted for coronary and peripheral angiography to evaluate angina pectoris and peripheral vascular disease. Following angiography, he suffered from blue toes, livedo reticularis and progressive renal failure. The patient's condition continued to deteriorate, including the development of malnutrition. Four months later he suddenly developed panperitonitis, went into shock and died. The autopsy verified multiple perforations of the small bowel with disseminated cholesterol atheromatous embolism. The other organs including kidney were also invaded by atheroembolism. This was a rare case of multiple spontaneous perforations of small bowel due to systemic cholesterol atheromatous embolism.

Intracellular generation of triiodothyronine (T3) from thyroxine (T4) by type 2 deiodinase (D2) in the mammalian brain, plays a key role in thyroid hormone action. The presence of D2 in rat astrocytes suggests the importance of glial cells in the regulation of intracellular T3 levels in the rat central nervous system (CNS). To analyze further the factors that regulate D2 activity in the CNS, we investigated the effects of nicotine and of mecamylamine, which inhibits the binding of nicotine with nicotinic acetylcholine receptors, on D2 activity in cultured mixed glial cells of the rat brain. We incubated cultured mixed glial cells obtained from neonatal Wistar rats in the presence of 10 mM dithiothreitol, 2 nM [125I] reverse T3 and 1 mM 6-N-propyl-2-thiouracil for 2 h at 37 degrees C, and the released 125I- was counted in a gamma counter. D2 activity of cultured cells was dependent on the temperature and the amount of protein. The basal D2 activity of rat mixed glial cells was 1.9 +/- 0.2 fmol of I- released/mg protein/h (mean +/- SEM). The addition of 10(-11), 2 x 10(-11), 10(-10), and 10(-9) M nicotine significantly increased D2 activity to approximately 2.2-, 2.4, 3.5- and 2.9-fold the basal level, respectively. D2 activity stimulated by 10(-8) M nicotine (2.5-fold) reached a peak after 9 h incubation. The stimulatory effect of nicotine was completely blocked by 10(-6) M mecamylamine. In conclusion, nicotine increases D2 activity probably via nicotinic acetylcholine receptors, and may influence brain function, at least in part, by affecting thyroid hormone metabolism.

To evaluate the age- and sex-related changes in Type 1 iodothyronine deiodinase gene expression in the liver and kidneys, we measured 5'-deiodinating activity and deiodinase mRNA in developing rats. The activity in the liver increased after birth, and that in neonates was approximately half that in adults. In contrast, the activity in neonatal kidneys remained very low. The relative importance of activity in male kidneys compared to the liver increased from the ages of 1 to 20 days. The male adult rat liver showed a higher level of activity than the female liver. Deiodinase mRNA in the male liver gradually increased from 1 to 20 days, in correlation with the activity. In kidneys, deiodinase mRNA was low before day 20, and there was no significant sex difference in all age groups. In orchiectomized male rats, the activity and mRNA in the liver was similar to the low levels found in females; however, the levels in the kidneys were not significantly different than those of normal males. These data suggest that the age- and sex-related changes in iodothyronine deiodinase gene expression are regulated mainly at the pretranslational level, and that the relative importance of kidneys to liver in iodothyronine deiodinase increases from birth to age 20 days due to the difference in the gene expression.

Serum coenzyme Q10 (CoQ10: 2-(3,7,11,15,19,23,27,31,35,39-decamethyl-2,6,10,14,18,22,26,30,34 ,38 -tetracontadecaenyl)-5,6-dimethoxy-3-methyl-1,4-benzoquinone, CAS 303-98-0) and cholesterol levels were measured to assess the effect of cholesterol-lowering therapy in patients with non-insulin-dependent diabetes mellitus (NIDDM). Twenty healthy volunteers, 97 NIDDM patients and 2 patients with familial hypercholesterolemia were studied. None had overt heart failure or any other heart disease. Mean serum CoQ10 concentrations were significantly (p < 0.01) lower in diabetic patients with normal serum cholesterol concentrations, either with or without administration of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (HMG-CoA RIs) including simvastatin (normal: 0.91 +/- 0.26 (mean +/- SD) mumol 1(-1); diabetic with HMG-CoA RI: 0.63 +/- 0.19; diabetic without HMG-CoA RI: 0.66 +/- 0.21). CoQ10 concentrations were higher (1.37 +/- 0.48, p < 0.001) in diabetic patients with hypercholesterolemia. Simvastatin or low density lipoprotein apheresis decreased serum CoQ10 concentrations along with decreasing serum cholesterol. Oral CoQ10 supplementation in diabetic patients receiving HMG-CoA RI significantly (p < 0.001) increased serum CoQ10 from 0.81 +/- 0.24 to 1.47 +/- 0.44 mumol 1(-1), without affecting cholesterol levels. It significantly (p < 0.03) decreased cardiothoracic ratios from 51.4 +/- 5.1 to 49.2 +/- 4.7%. In conclusion, serum CoQ10 levels in NIDDM patients are decreased and may be associated with subclinical diabetic cardiomyopathy reversible by CoQ10 supplementation.

A 30-year-old pregnant woman complained of muscle weakness at 29 weeks' gestation. She was hypertensive with severe hypokalemia. Lower plasma renin activity and higher aldosterone level than the normal values in pregnancy suggested primary aldosteronism. A cesarean delivery was performed at 31 weeks' gestation because of pulmonary congestion. The neonatal course was uncomplicated. The laparoscopic adrenalectomy for a 2.0-cm right adrenal adenoma resulted in normalizing of her blood pressure and serum potassium level. Although primary aldosteronism is rare, especially during pregnancy, it should be always considered as one of etiologies of hypertension in pregnancy.

We investigated the effects of cyclic guanosine 3',5'-monophosphate (cGMP) on type 2 iodothyronine deiodinase (D2) in cultured rat glial cells. Rat glial cells were cultured in Dulbecco's modified Eagle's medium supplemented with 15% fetal bovine serum. When cells were cultured in the presence of 8-bromo cGMP (8-Br cGMP), an analogue of cGMP, D2 activity was increased in a time- and concentration-dependent manner. Lineweaver-Burk plots revealed that the stimulation of D2 activity by 8-Br cGMP (10(-3) M) was associated with fivefold increase in maximum velocity but without a significant change in Michaelis-Menten constant, suggesting that cGMP increases D2 activity via new enzyme synthesis. Both atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) are well known to increase the intracellular cGMP level via their guanylate cyclase-linked receptors in rat glial cells. In the present study, ANP (10(-6) M) and CNP (10(-6) M) significantly increased the D2 activity in rat glial cells (1.9-fold [ANP] or 2.3-fold [CNP] compared with control activity, respectively). Northern blot analysis demonstrated that D2 mRNA level increased in the presence of 8-Br cGMP (10(-3) M), and reached a plateau (six-fold) after 4 hours of incubation. The increment of D2 mRNA level by 8-Br cGMP was comparable with the increase of the D2 activity by this agent. Our data suggest that cGMP induces rat D2 activity, at least in part, at the pretranslational level, and that ANP and CNP increase D2 activity most likely via their guanylate cyclase-linked receptors in rat glial cells.

To investigate the possible humoral factor(s) influencing thyroid cell activity in chronic renal failure, we measured serum activity which stimulates or inhibits the [3H]thymidine incorporation by using a cultured functioning rat thyroid cell line (FRTL-5 cells) in 17 patients on hemodialysis and 19 healthy controls. Polyethylene glycol-treated serum was centrifuged and FRTL-5 cells were cultured with the supernatant. Thyroid stimulating activity was determined by [3H]thymidine incorporation after incubation for 72 h. There was no significant difference in [3H]thymidine incorporation between cultures incubated with patient and normal serum, suggesting the absence of the stimulating activity. But when patient serum was added to cultures together with 20 or 50 microU/ml of TSH, the TSH-stimulated increase in [3H]thymidine incorporation was significantly decreased, indicating the presence of thyroid inhibiting activity, which possibly inhibits the thyroid cell growth. This activity was not significantly altered by hemodialysis. No significant correlation was observed between this activity and serum levels of thyroid hormones or the iodine concentration. Patients on hemodialysis therefore have serum thyroid inhibiting activity which is nondialysable, differs from iodine, and could influence the thyroid cell growth.

A nine-year old boy developed reduced growth velocity at the age of seven. The peak plasma growth hormone (GH) response to 3,4-dihydroxyphenylalanine, GH-releasing factor and insulin was 10.2, 8.1 and 7.6 micrograms/l, respectively, suggesting that the GH reserve was slightly reduced. Serum cortisol was undetectable and urinary excretion of 17-hydroxycorticosteroid was low (0.22-0.31 mg/day), but there were no physical or biochemical signs of adrenocortical insufficiency. He had taken an anti-allergic drug containing 0.25 mg of betamethasone and 2 mg of d-chlorpheniramine maleate per tablet for about 2 years to treat allergic rhinitis. Catch-up growth occurred when this drug was stopped. The present case suggests that daily administration of 0.25 mg of betamethasone can induce growth retardation and that ingestion of corticosteroid-containing preparations needs to be excluded in children who develop short stature without other symptoms.

Since thyroid hormones have been reported to increase the synthesis of rat atrial natriuretic hormone and its mRNA accumulation, we further investigated the mechanism of stimulation of rANH synthesis by T3 using cultured rat atrial myocytes. T3 (10−9-10−7 mol/l) increased cellular content and secretion into the medium of immunoreactive rANH in a dose-dependent manner. However, the ratio of secreted/cellular rANH was not altered by the addition of T3. Furthermore, in both cellular and secreted rANH, the larger molecular form (γ-rANH) apparently predominated over the smaller one (α-rANH), and this profile was not influenced by T3 (10−7 mol/l). Although T3 (10−9-10−7 mol/l) also increased cellular rANH mRNA accumulation, the ratio of cellular rANH/rANH mRNA was not changed. Moreover, using actinomycin D, we found that T3 (10−7 mol/l) did not affect the degradation of rANH mRNA. From these findings, we suggest that T3 has no specific effects on the translational and posttranslational processes and the release of rANH, but that T3 stimulates rANH synthesis in the pretranslational levels, probably in the transcriptional level of rANH gene.

Using a primary culture of neonatal rat heart, we investigated the properties of iodothyronine 5'-deiodinating activity in the heart. 125I- release from [125I] reverse T3 incubated with cell homogenates depended on the concentrations of protein and dithiothreitol, pH, incubation time, and temperature of the incubation mixture. The activity was almost completely inhibited by 10(-3)-10(-5) M propylthiouracil and had the higher affinity for reverse T3 than T4. These findings indicate that type I iodothyronine 5'-deiodinase(I-5'-D) exists in cultured neonatal rat myocardial cells. Then, we studied the direct effects of T3, insulin, glucocorticoid, and angiotensin II (AII) on myocardial I-5'-D. The addition of 10(-9)-10(-7) M T3 or 10(-9)-10(-6) M AII to the culture medium increased I-5'-D activity in a dose-dependent manner. Insulin and dexamethasone, however, had no significant effects. Kinetic studies revealed that maximum velocities in T3- and AII-treated cells were 2.1- and 1.8-fold above the control value, respectively, whereas the apparent Michaelis-Menten constant did not alter significantly both in T3- and AII-treated cells. Moreover, the treatment of cyclohexamide combined with T3 or AII completely abolished the stimulating effect of these agents on I-5'-D activity. From these data, it is suggested that both T3 and AII increase the activity of myocardial I-5'-D by their direct actions to the heart, probably through the new synthesis of I-5'-D.