Thyroid hormone increases mannan-binding lectin levels

Background: Recent studies have indicated the existence of causal links between the endocrine and immune systems and cardiovascular disease. Mannan-binding lectin (MBL), a protein of the innate immune system, may constitute a connection between these fields. Methods: To test whether thyroid hormone regulates MBL levels, we studied eight patients with Graves’ hyperthyroidism before and after methimazole therapy, eight healthy subjects before and after short-term experimental hyperthyroidism, and eight hypothyroid patients with chronic auto-immune thyroiditis before and after L-thyroxine substitution. Results: In all hyperthyroid patients, MBL levels were increased – median (range), 1886 ng/ml (1478–7344) – before treatment and decreased to 954 ng/ml (312–3222) after treatment (P = 0.01, paired comparison: Wilcoxon’s signed ranks test). The healthy subjects had MBL levels of 1081 ng/ml (312–1578). Administration of thyroid hormones to these persons induced mild hyperthyroidism and increased MBL levels significantly to 1714 ng/ml (356–2488) (P = 0.01). Two of the eight hypothyroid patients had undetectably low levels of MBL both before and after L-thyroxine substitution. The other six hypothyroid patients had decreased levels of MBL of 145 ng/ml (20–457) compared with 979 ng/ml (214–1533) after L-thyroxine substitution (P = 0.03, paired comparison: Wilcoxon’s signed ranks test). Conclusion: Our data show that thyroid hormone increases levels of MBL. MBL is part of the inflammatory complement system, and this modulation of complement activation may play a role in the pathogenesis of a number of key components of thyroid diseases.

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Urine TRH immunoreactivity in hypothyroid and hyperthyroid patients

Acta Endocrinologica ◽

10.1530/acta.0.1050482 ◽

1984 ◽

Vol 105 (4) ◽

pp. 482-486 ◽

Cited By ~ 2

Author(s):

Anna-Stina Suhonen ◽

Juhani Leppäluoto ◽

Jorma Salmi

Keyword(s):

Healthy Subjects ◽

Ammonium Acetate ◽

Polar Solvent ◽

Primary Hypothyroidism ◽

Exchange Chromatography ◽

Reverse Phase ◽

Before And After ◽

Hypothyroid Patients ◽

Hyperthyroid Patients ◽

Serum Tsh

Abstract. Urine samples from 8 healthy subjects, from 16 patients with primary hypothyroidism and 8 patients with Graves' hyperthyroidism were pre-purified in SP-Sephadex-C-25 cation-exchange-chromatography, subjected to reverse phase high-pressure liquid chromatography (HPLC) with 0.01 M ammonium acetate pH 4 as a polar and propanol as a non-polar solvent with a 1%/min gradient and assayed in our TRH radioimmunoassay. Urine TRH-immunoreactivity levels were measured before and after 3 months of treatment with thyroxine or methimazole. The urine TRH-levels in healthy subjects were 5.5 ± 1.4 ng/l (mean ± sem, n = 8). In the hypothyroid patients, the urine TRH levels were 50.6 ±40 ng/l before and 71.7 ± 45.3 ng/l after 3 months of treatment with thyroxine. These values did not significantly differ from those in healthy subjects. The large variations were due to highly elevated values in 3 patients. In 2 hypothyroid patients with initially high urine TRH values, 67 and 657 ng/l, urine TRH was measured 5 and 18 months later and was found to have decreased to 5 and 11 ng/l. In the hyperthyroid patients, urine TRH levels were 10.3 ± 3.9 ng/l before and 8.9 ± 3.3 ng/l after the treatment with methimazole and did not differ significantly from the levels in healthy subjects. After 3 months of treatment, the hyper- and the hypothyroid patients were euthyroid. Our results show, that, except in 2 hypothyroid patients, there does not appear to be any relationship between urine TRH levels and serum TSH or thyroid hormone levels in hypothyroid and hyperthyroid patients.

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Serum 3'-monoiodothyronine levels in normal subjects and in patients with thyroid and non-thyroid disease

Acta Endocrinologica ◽

10.1530/acta.0.0970454 ◽

1981 ◽

Vol 97 (4) ◽

pp. 454-460 ◽

Cited By ~ 1

Author(s):

C. Kirkegaard ◽

J. Faber ◽

D. Cohn ◽

K. Kølendorf ◽

H. Francis Thomsen ◽

...

Keyword(s):

Healthy Subjects ◽

Normal Subjects ◽

Serum Levels ◽

Endogenous Depression ◽

Lower Detection Limit ◽

Specific Radioimmunoassay ◽

Lower Detection ◽

Before And After ◽

Hypothyroid Patients ◽

Hyperthyroid Patients

Abstract. Serum 3'-monoiodothyronine (3'-T1) levels were estimated by means of a specific radioimmunoassay (RIA) preceded by an ethanol extraction. The recovery of 3'-T1 was in mean (± sem) 110 ± 9%, and the lower detection limit was 23 pmol/l. Serum levels of 3'-T1 in 34 euthyroid healthy subjects were (median (range)) 55 pmol/l (<23-168 pmol/l), in 13 hyperthyroid patients 133 pmol/l (70-265 pmol/l) (P < 0.01) and in 13 hypothyroid patients <23 pmol/l (<23-68 pmol/l) (P <0.01). In 11 patients with chronic renal failure serum 3'-T1 levels were highly increased 285 pmol/l (115-1538 pmol/l) (P < 0.01) and correlated inversely to creatinine clearance (R = −0.68, P < 0.05). In patients with liver cirrhosis serum 3'-T1 levels were unaffected, whereas in 19 patients with endogenous depression studied before and after recovery from the depression serum levels decreased from 70 pmol/l (< 23-248 pmol/l) to 30 pmol/l (<23-95 pmol/l (P < 0.01). Administration of propranolol 40 mg b. i. d. for 2 weeks did not affect serum 3'-T1 levels. The study shows that 3'-T1 is present in serum from euthyroid man and varies with thyroid function. Further, it is suggested that 3'-T1 in contrast to other iodothyronines primarily is eliminated by the kidneys.

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Recombinant mannan-binding lectin (MBL) for therapy

Biochemical Society Transactions ◽

10.1042/bst0310763 ◽

2003 ◽

Vol 31 (4) ◽

pp. 763-767 ◽

Cited By ~ 58

Author(s):

J.C. Jensenius ◽

P.H. Jensen ◽

K. McGuire ◽

J.L. Larsen ◽

S. Thiel

Keyword(s):

Immune Response ◽

Clinical Trials ◽

Clinical Evidence ◽

Human Cell Line ◽

Innate Immune ◽

Genetically Determined ◽

Micro Organisms ◽

Mannan Binding Lectin ◽

Binding Lectin ◽

Increased Susceptibility

Mannan-binding lectin (MBL) is a plasma protein involved in the innate immune response. It binds to a number of micro-organisms and promotes killing of these through complement activation either directly or through opsonization. Clinical evidence indicates that in a variety of situations genetically determined low MBL levels are associated with increased susceptibility to infections. Infusions of plasma-derived MBL into MBL-deficient individuals was found to be safe in preliminary trials, but we considered that sufficient production and product safety could only be achieved through synthesis of recombinant MBL. A transfected human cell line produces MBL showing the same biological activity as plasma-derived MBL, and an essentially identical profile on MS. The production has been scaled up and clinical trials will start this year.

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Association of three systemic lupus erythematosus susceptibility factors, PD-1.3A, C4AQ0, and low levels of mannan-binding lectin, with autoimmune manifestations in icelandic multicase systemic lupus erythematosus families

Arthritis & Rheumatism ◽

10.1002/art.24129 ◽

2008 ◽

Vol 58 (12) ◽

pp. 3865-3872 ◽

Cited By ~ 8

Author(s):

Helga Kristjansdottir ◽

Saedis Saevarsdottir ◽

Gerdur Gröndal ◽

Marta E. Alarcón-Riquelme ◽

Kristjan Erlendsson ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Systemic Lupus ◽

Systemic Lupus Erythematosus Susceptibility ◽

Susceptibility Factors ◽

Low Levels ◽

Mannan Binding Lectin ◽

Binding Lectin

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THYROID FUNCTION AND PLASMA CYCLIC AMP RESPONSE TO INTRAVENOUS GLUCAGON

Acta Endocrinologica ◽

10.1530/acta.0.0850760 ◽

1977 ◽

Vol 85 (4) ◽

pp. 760-768 ◽

Cited By ~ 11

Author(s):

S. Nistrup Madsen

Keyword(s):

Cyclic Amp ◽

Thyroid Hormones ◽

Thyroid Function ◽

Healthy Subjects ◽

Blood Levels ◽

Sensitive Test ◽

Normal Response ◽

Hypothyroid Patients ◽

Hyperthyroid Patients

ABSTRACT The glucagon stimulated increase in plasma cyclic AMP has been studied in 17 healthy subjects, in 13 hyperthyroid and in 14 hypothyroid patients. Six hyperthyroid and 2 hypothyroid patients were re-investigated after at least 15 months of treatment. The results show: 1) The glucagon stimulated cyclic AMP response is significantly increased in hyperthyroid patients considered as a group, and is reduced in patients with hypothyroidism. 2) Three hyperthyroid and 4 hypothyroid patients showed a normal response to iv glucagon, indicating that the plasma cyclic AMP response to iv glucagon is not a sensitive test for the evaluation of peripheral thyroid states. This suggests that the effects of thyroid hormones in the liver does not necessarily follow the effects in other tissues. 3) Re-investigation of treated patients showed that the cyclic AMP response can be normalized by treatment, both in hyperthyroidism and in hypothyroidism. However, in patients treated for hyperthyroidism a hyper-response to glucagon can continue after blood levels of thyroid hormones are reduced to normal. This suggests an inertia in the loss of the hyper-response to glucagon, once a hyperfunction has been induced. A similar inertia in the loss of glucagon sensitivity in hypothyroidism could explain the large number of normal tests in hypothyroid patients.

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Innate Immune Proteins C1q and Mannan-Binding Lectin Enhance Clearance of Atherogenic Lipoproteins by Human Monocytes and Macrophages

The Journal of Immunology ◽

10.4049/jimmunol.1002080 ◽

2010 ◽

Vol 185 (7) ◽

pp. 3932-3939 ◽

Cited By ~ 42

Author(s):

Deborah A. Fraser ◽

Andrea J. Tenner

Keyword(s):

Innate Immune ◽

Human Monocytes ◽

Monocytes And Macrophages ◽

Mannan Binding Lectin ◽

Binding Lectin ◽

Human Monocytes And Macrophages

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THE INFLUENCE OF HYPOPHYSECTOMY ON NSILA CONCENTRATIONS IN THE DOG: EVIDENCE FOR PARTIALLY PITUITARY-INDEPENDENT REGULATION

Acta Endocrinologica ◽

10.1530/acta.0.0860498 ◽

1977 ◽

Vol 86 (3) ◽

pp. 498-503 ◽

Cited By ~ 4

Author(s):

J. E. Eigenmann ◽

M. Becker ◽

B. Kammermann ◽

J. Zapf ◽

W. Leemann ◽

...

Keyword(s):

Growth Hormone ◽

Thyroid Hormone ◽

Pituitary Gland ◽

Normal Level ◽

Binding Assay ◽

Serum Samples ◽

Protein Binding Assay ◽

Before And After ◽

Low Levels ◽

Insulin Like Activity

ABSTRACT Non-suppressible insulin-like activity (NSILA) was determined in 5 dogs before and after hypophysectomy. All NSILA determinations were carried out on serum samples after acidic Sephadex G-50 chromatography by two different assay systems, i. e. a bioassay and a protein binding assay. The levels of NSILA decreased significantly after hypophysectomy and returned to near normal levels after 2 weeks. T3−, T4− and cortisol levels were drastically reduced during the entire period of the experiment. Several GH determinations after hypophysectomy revealed very low levels. Insulin-induced hypoglycaemia failed to provoke a rise of GH levels as late as 4 months after hypophysectomy. These findings indicate that: 1) The pituitary gland cannot be the site of synthesis of NSILA. 2) NSILA concentrations in the dog are maintained at a near normal level in the presence of very low growth hormone and thyroid hormone concentrations, so that these latter hormones do not appear to be the only regulatory factors concerned in NSILA synthesis.

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Thyroid Hormone Increases mRNA and Protein Expression of Na+-K+-ATPase α2 and β1 Subunits in Human Skeletal Muscles

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-0552 ◽

2007 ◽

Vol 92 (1) ◽

pp. 353-358 ◽

Cited By ~ 8

Author(s):

Bunyong Phakdeekitcharoen ◽

Suchart Phudhichareonrat ◽

Chathchai Pookarnjanamorakot ◽

Chusak Kijkunasathian ◽

Nattha Tubtong ◽

...

Keyword(s):

Thyroid Hormone ◽

Protein Expression ◽

Mrna Expression ◽

Skeletal Muscles ◽

Vastus Lateralis ◽

Mrna Level ◽

Before And After ◽

Hyperthyroid Patients ◽

Relative Mrna Expression ◽

Human Skeletal Muscles

Abstract Context: Thyroid hormone regulates specific Na+-K+-ATPase isoforms in rodent skeletal muscles. No study has examined this relationship in human tissues. Objective: This study investigated the effect of hyperthyroid status on the expression of the α- and β-subunits of the Na+-K+-ATPase. Design: The vastus lateralis muscles from eight hyperthyroid patients were biopsied before and after treatment. Ten age-matched euthyroid subjects served as controls. Results: In hyperthyroid patients, the average T3 level was three times higher in pretreatment compared with posttreatment (262 ± 75 vs. 86 ± 21 ng/dl, P = 0.001). The relative mRNA expression of the α2, but not α1 or α3, subunit was increased approximately 3-fold in pretreatment (2.98 ± 0.52 vs. 0.95 ± 0.40, P < 0.01), whereas that of β1, not β2 or β3, subunit was increased approximately 2.8-fold in pretreatment (2.83 ± 0.38 vs. 1.10 ± 0.27, P < 0.01). The relative mRNA expression of the α2 and β1 subunits was positively correlated with the serum T3 (r = 0.75, P = 0.001 and r = 0.66, P = 0.003, respectively). Immunohistochemistry studies revealed an increase in protein abundance of the α2 and β1, but not α1 or β2, subunits in the plasma membrane of muscle fibers of hyperthyroid patients, which decreased after treatment. Conclusions: This provides the first evidence that, in human skeletal muscles, thyroid hormone up-regulates the Na+-K+-ATPase protein expression at least, in part, at mRNA level, and the α2 and β1 subunits play the important role in this regulation.

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