Calcitonin gene-related peptide as a GH secretagogue in human and rat pituitary somatotrophs

Nakamura, Yoshio; Shimatsu, Akira; Murabe, Hiroyuki; Mizuta, Haruo; Ihara, Chihiro; Nakao, Kazuwa

doi:10.1016/s0006-8993(98)00776-8

Cited by 22 publications

(11 citation statements)

References 30 publications

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“…We could demonstrate AM gene activity in all tumour entities, and relatively high mRNA content was found in somatotropic adenomas. AM may execute a regulatory function in these tumours, since AM is able to evoke growth hormone secretion in normal rat pituitary cells and somatotropinomas [21]. AM exhibits vasodilatory properties and may be of additional value for tumours by increasing blood flow within the tumour bed.…”

Section: Discussionmentioning

confidence: 99%

Gene expression of adrenomedullin, leptin, their receptors and neuropeptide Y in hormone‐secreting and non‐functioning pituitary adenomas, meningiomas and malignant intracranial tumours in humans

Knerr

Schuster²,

Nomikos

et al. 2001

Neuropathology Appl Neurobio

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The aim of this study was to assess human intracranial tumours for their gene expression pattern of the vasoactive peptide adrenomedullin (AM), its receptor (AM-R) and leptin, which exerts multiple biological effects including proliferation and angiogenesis via the leptin receptor (OB-Rb). Gene activity of neuropeptide Y (NPY) was monitored additionally. We investigated whether there was a characteristic gene expression pattern of AM and leptin in different intracranial tumours, depending on their proliferation activity and biological behaviour. We investigated 35 non-functioning pituitary adenomas (including eight null cell, four silent plurihormonal, 23 silent gonadotroph adenomas), seven somatotropinomas, seven prolactinomas, eight meningiomas, five astrocytomas, two glioblastoma multiformes and unaffected temporal lobe (n = 8). Quantitative reverse transcriptase-polymerase chain reaction (TaqMan RT-PCR) was performed. AM mRNA was detectable in all tumour specimens. AM/GAPDH (glyceraldehyde-3-phosphate dehydrogenase) ratio was significantly higher in somatotropinomas, as was AM/CD31 ratio in prolactinomas, compared with inactive adenomas (P < 0.05). AM-R mRNA was found in all tumour subgroups in small quantities but, in general, higher in tumours than in temporal lobe tissue, respectively. AM-R/CD31 ratio was significantly higher in prolactinomas than in inactive adenomas (P < 0.05). Leptin was detectable in very low quantities in each subgroup. OB-Rb gene expression was found in all tumour subgroups, OB-Rb/GAPDH ratio was highest for meningiomas (P < 0.0001, compared with temporal lobe). NPY mRNA was detectable in temporal lobe in higher quantities than in tumours (P < 0.0001), and almost undetectable in prolactinomas and astrocytomas. Our data demonstrate that AM and AM-R, NPY, as well as leptin and OB-Rb, are expressed in various intracranial tumours in humans but their particular function has to be elucidated further. At present, there is no evidence for a cross-talk on transcriptional level between the peptidergic vasodilative system AM and the putative angiogenic and proliferation affecting factor leptin.

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Section: Discussionmentioning

confidence: 99%

Gene expression of adrenomedullin, leptin, their receptors and neuropeptide Y in hormone‐secreting and non‐functioning pituitary adenomas, meningiomas and malignant intracranial tumours in humans

Knerr

Schuster²,

Nomikos

et al. 2001

Neuropathology Appl Neurobio

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“…Furthermore, there have been some reports suggesting that AM2/IMD might act on receptor systems other than CRLR/RAMPs, particularly in the hypothalamus and/or pituitary [29]. Contrary to previous findings that AM2/IMD elevated intracellular cAMP levels [1,3] and that CGRP stimulated growth hormone secretion in rats and humans [30], Taylor et al revealed that AM2/IMD inhibited growth hormone release in Sprague‐Dawley rats [29]. There were no reports about the existence of such unidentified AM2/IMD unique receptors in peripheral tissues.…”

Section: Discussionmentioning

confidence: 96%

Increased expression of adrenomedullin 2/intermedin in rat hearts with congestive heart failure

Hirose

Totsune

Mori

et al. 2008

European J of Heart Fail

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Adrenomedullin 2/intermedin (AM2/IMD) is a novel member of the calcitonin/calcitonin gene-related peptide family. To investigate the pathophysiological role of AM2/IMD in heart failure, we examined the expression of AM2/IMD, adrenomedullin (AM) and receptor complex components (calcitonin receptor-like receptor, three types of receptor activity-modifying proteins) by quantitative RT-PCR and immunohistochemistry in the hearts and kidneys of rats with congestive heart failure (CHF). Significantly increased levels of AM2/IMD mRNA were found in the atrium, right ventricle, non-infarcted part of the left ventricle and the infarcted part of the left ventricle of CHF rats, compared with sham operated rats (about 2.8-fold, 1.7-fold, 1.7-fold and 2.5-fold, respectively). Expression levels of mRNA encoding AM and the receptor complex components were also increased in the hearts of CHF rats. In a separate experiment, AM2/IMD mRNA levels in the heart did not differ between Wistar-Kyoto and spontaneously hypertensive rats. In both sham operated and CHF rats, the myocardium was diffusely immunostained with AM2/IMD. The fibrotic infarcted layer was not immunostained with AM2/IMD but was surrounded by positively immunostained myocardial layers. These findings suggest that the expression of AM2/IMD is enhanced in the failing heart, and AM2/IMD has a certain pathophysiological role in heart failure.

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“…Indeed, AM dose-dependently inhibits adrenocorticotropic hormone (ACTH) release and attenuates CRH-stimulated ACTH production from primary cultures of rat anterior pituitary cells [63]. This effect is also evident in vivo [64]. These findings suggest that AM functions in inhibiting ACTH release.…”

Section: -4 Endocrine Action Of Ammentioning

confidence: 94%

Adrenomedullin in Heart Failure: Molecular Mechanism and Therapeutic Implication

Nishikimi¹,

Nakao²,

Kangawa

2011

CHYR

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Many neurohumoral factors play an important role in regulation of the cardiovascular system and in the pathophysiology of heart failure. Adrenomedullin (AM) is a potent long-lasting vasodilatory peptide that was discovered in acid extracts of human pheochromocytoma tissues. Both AM and its gene expression are widely distributed in the cardiovascular system, including the heart, vessels, and kidneys. AM co-localizes with its receptor components such as calcitonin receptor-like receptor (CRLR), receptor activity modifying protein (RAMP)2 and RAMP3 in the heart, vessels and kidneys, suggesting that it plays an important role in the regulation of cardiovascular function through an autocrine and/or paracrine mechanism. AM has inotropic action in vitro and in vivo and inhibits cardiac hypertrophy in myocytes as well as proliferation and collagen production in cardiac fibroblasts. These results suggest that AM functions as an antifibrotic, antihypertrophic and positive inotropic factor in the failing heart. In addition, AM has anti-apoptotic, angiogenic, anti-inflammatory and anti-oxidant effects. Several mechanisms such as cAMP/PKA, NO/cGMP, PI-3K/Akt and/or ERK are thought to mediate cellular AM signaling, suggesting that increased AM levels play a protective role in heart failure. Indeed, acute AM administration exerts beneficial vasodilatory, diuretic, natriuretic and inotropic effects on experimental and human heart failure. A recent pilot study has shown that AM has potential as a therapeutic drug in the clinical setting of acute decompensated heart failure.

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Calcitonin gene-related peptide as a GH secretagogue in human and rat pituitary somatotrophs

Cited by 22 publications

References 30 publications

Gene expression of adrenomedullin, leptin, their receptors and neuropeptide Y in hormone‐secreting and non‐functioning pituitary adenomas, meningiomas and malignant intracranial tumours in humans

Gene expression of adrenomedullin, leptin, their receptors and neuropeptide Y in hormone‐secreting and non‐functioning pituitary adenomas, meningiomas and malignant intracranial tumours in humans

Increased expression of adrenomedullin 2/intermedin in rat hearts with congestive heart failure

Adrenomedullin in Heart Failure: Molecular Mechanism and Therapeutic Implication

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