Elevation of circulating proadrenomedullin‐N terminal 20‐peptide in thyrotoxicosis

Taniyama, Matsuo; Kïtamura, Kazuo; Ban, Yoshio; Sugita, Eri; Ito, Kunihiko; Kubo, Takashi

doi:10.1046/j.1365-2265.1997.1220934.x

Cited by 19 publications

(3 citation statements)

References 23 publications

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“…It is also known that adm levels increase in hyperthyroid human patients [60], [61], but the molecular basis of the latter effect have not been previously characterized. We confirmed that T3-dependent transcriptional activation of human adm was unabated by the translation inhibitor CHX in TRβ-BioChIP cells, proving that it is a direct target (Fig.…”

Section: Resultsmentioning

confidence: 99%

Genome-Wide Binding Patterns of Thyroid Hormone Receptor Beta

et al. 2014

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Thyroid hormone (TH) receptors (TRs) play central roles in metabolism and are major targets for pharmaceutical intervention. Presently, however, there is limited information about genome wide localizations of TR binding sites. Thus, complexities of TR genomic distribution and links between TRβ binding events and gene regulation are not fully appreciated. Here, we employ a BioChIP approach to capture TR genome-wide binding events in a liver cell line (HepG2). Like other NRs, TRβ appears widely distributed throughout the genome. Nevertheless, there is striking enrichment of TRβ binding sites immediately 5′ and 3′ of transcribed genes and TRβ can be detected near 50% of T3 induced genes. In contrast, no significant enrichment of TRβ is seen at negatively regulated genes or genes that respond to unliganded TRs in this system. Canonical TRE half-sites are present in more than 90% of TRβ peaks and classical TREs are also greatly enriched, but individual TRE organization appears highly variable with diverse half-site orientation and spacing. There is also significant enrichment of binding sites for TR associated transcription factors, including AP-1 and CTCF, near TR peaks. We conclude that T3-dependent gene induction commonly involves proximal TRβ binding events but that far-distant binding events are needed for T3 induction of some genes and that distinct, indirect, mechanisms are often at play in negative regulation and unliganded TR actions. Better understanding of genomic context of TR binding sites will help us determine why TR regulates genes in different ways and determine possibilities for selective modulation of TR action.

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Section: Resultsmentioning

confidence: 99%

Genome-Wide Binding Patterns of Thyroid Hormone Receptor Beta

et al. 2014

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“…Transcription yields a precursor peptide, proadrenomedullin, from which ADM and PAMP are enzymatically cleaved. Both peptides have a similar widespread tissue distribution throughout the body [3], and are present in plasma in healthy subjects in concentrations of ∼5–10 pmol l −1 [4, 5]. In addition, ADM is actively synthesized and secreted by human vascular endothelial and smooth muscle cells, which also possess ADM receptors [3, 6, 7].…”

Section: Introductionmentioning

confidence: 99%

Adrenomedullin (ADM) in the human forearm vascular bed: effect of neutral endopeptidase inhibition and comparison with proadrenomedullin NH₂‐terminal 20 peptide (PAMP)

Wilkinson¹,

McEniery²,

Bongaerts³

et al. 2001

Brit J Clinical Pharma

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Aims To compare the haemodynamic responses of proadrenomedullin N-terminal 20 peptide (PAMP) and adrenomedullin (ADM) in the forearm vascular bed of healthy male volunteers, and to investigate the role of neutral endopeptidase (NEP) in the metabolism of ADM. Methods On two separate occasions, ADM (1±30 pmol min x1 ) and PAMP (100±3000 pmol min x1 ) were infused into the brachial artery of eight male subjects, and forearm blood¯ow (FBF) assessed using venous occlusion plethysmography. In a second study, eight male subjects received the same doses of ADM, co-infused with either the NEP inhibitor thiorphan (30 nmol min x1 ) or the control vasoconstrictor noradrenaline (120 pmol min x1 ), on separate occasions. Both studies were conducted in a double-blind, randomized manner. Results ADM and PAMP produced a dose-dependent increase in FBF (Pj0.002). Based on the dose producing a 50% increase in FBF, ADM was y60 times more potent than PAMP. Thiorphan and noradrenaline produced similar reductions in FBF of 14t4% (mean t s.e. mean) and 22t6%, respectively (P=0.4). However, the area under the dose±response curve was signi®cantly greater during co-infusion of ADM with thiorphan than with noradrenaline (P=0.028), as was the maximum increase in FBF ratio (2.1t1.0 vs 1.2t0.2; P= 0.030). Conclusions ADM and PAMP both produce a local dose-related vasodilatation in the human forearm, but PAMP is y60 times less potent than ADM. In addition, NEP inhibition potentiates the haemodynamic effects of ADM. These ®ndings suggest that PAMP may not play a role in the physiological regulation of blood¯ow. However, in pathophysiological conditions such as hypertension and heart failure, NEP inhibition may exert a bene®cial effect by increasing the biological activity of ADM.

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“…Current evidence is that peptide levels in plasma are raised in patients with impaired renal function, 19,20 in some patients with essential hypertension or primary aldosteronism, [21][22][23] in poorly controlled diabetics, 24 after acute myocardial infarction, 25 in congestive heart failure in proportion to the severity of cardiac dysfunction, 26 -28 and in thyrotoxicosis. 29,30 Levels are also increased through normal pregnancy, 31 but according to Hata and colleagues this rise is not seen in patients with preeclampsia. 32 Markedly elevated levels have been recorded across hypothermic cardiopulmonary bypass, 33 in patients with a variety of severe illnesses, 34 and particularly in sepsis.…”

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confidence: 99%

The role of adrenomedullin

Charles

Lainchbury

Lewis

et al. 1999

American Journal of Hypertension

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Elevation of circulating proadrenomedullin‐N terminal 20‐peptide in thyrotoxicosis

Abstract: Elevation of the plasma adrenomedullin and proadrenomedullin-N terminal 20-peptide levels raises the possibility of involvement of these vasodilatory peptides in the haemodynamic changes in thyrotoxicosis.

Cited by 19 publications

References 23 publications

Genome-Wide Binding Patterns of Thyroid Hormone Receptor Beta

Genome-Wide Binding Patterns of Thyroid Hormone Receptor Beta

Adrenomedullin (ADM) in the human forearm vascular bed: effect of neutral endopeptidase inhibition and comparison with proadrenomedullin NH₂‐terminal 20 peptide (PAMP)

The role of adrenomedullin

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Elevation of circulating proadrenomedullin‐N terminal 20‐peptide in thyrotoxicosis

Abstract: Elevation of the plasma adrenomedullin and proadrenomedullin-N terminal 20-peptide levels raises the possibility of involvement of these vasodilatory peptides in the haemodynamic changes in thyrotoxicosis.

Cited by 19 publications

References 23 publications

Genome-Wide Binding Patterns of Thyroid Hormone Receptor Beta

Genome-Wide Binding Patterns of Thyroid Hormone Receptor Beta

Adrenomedullin (ADM) in the human forearm vascular bed: effect of neutral endopeptidase inhibition and comparison with proadrenomedullin NH2‐terminal 20 peptide (PAMP)

The role of adrenomedullin

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Adrenomedullin (ADM) in the human forearm vascular bed: effect of neutral endopeptidase inhibition and comparison with proadrenomedullin NH₂‐terminal 20 peptide (PAMP)