Participation of adrenomedullin and its relation with vascular endothelial growth factor in androgen regulation of prostatic blood flow in vivo

Shibata, Yasuhiro; Kashiwagi, Bunzo; Arai, Seiji; Magari, Tomohiro; Suzuki, Kazuhiro; Honma, Sato

doi:10.1016/j.urology.2006.06.025

Cited by 6 publications

(4 citation statements)

References 33 publications

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“…It was previously shown that down regulation of VEGF or its receptor, VEGFR-2, could not suppress AM induced angiogenesis [30]. Interestingly, an AM antagonist was able to inhibit VEGF induced blood flow [32]. Our data suggests that AM acts as an VEGF-independent angiogenic factor and a reduction in AM's function in cancer cells and the adjacent tumor microenvironment cells results in reduced neoangiogenesis.…”

Section: Discussionmentioning

confidence: 47%

The ADMR Receptor Mediates the Effects of Adrenomedullin on Pancreatic Cancer Cells and on Cells of the Tumor Microenvironment

et al. 2009

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BackgroundAdrenomedullin (AM) is highly expressed in pancreatic cancer and stimulates pancreatic cancer cells leading to increased tumor growth and metastasis. The current study examines the role of specific AM receptors on tumor and cells resembling the tumor microenvironment (human pancreatic stellate - HPSC, human umbilical vein – HUVEC and mouse lung endothelial cells - MLEC).Methods and FindingsAM receptors ADMR and CRLR were present in HPSC, HUVEC and MLECs while PDAC cells possessed only ADMR receptors as assessed by RT-PCR and western blotting. All cell lines expressed and secreted AM as indicated by ELISA. The growth of each of the cell lines was stimulated by exogenous AM and inhibited by the antagonist AMA. AM also stimulated in vitro angiogenesis assessed by polygon formation of endothelial cell lines. SiRNA-mediated silencing of ADMR, but not CRLR, reduced basal growth of all cells examined and reduced polygon formation of endothelial cells in vitro. Orthotopic tumors developed with shADMR bearing cancer cells had dramatically reduced primary tumor volume (>90%) and lung and liver metastasis compared to shControl bearing cells. To validate ADMR as a potential therapeutic target, in vivo studies were conducted using neutral nanoliposomes to systemically deliver human siRNA to ADMR to silence human cancer cells and mouse siRNA to ADMR to silence mouse tumor stromal cells. Systemic silencing of both human and mouse ADMR had no obvious adverse effects but strongly reduced tumor development.ConclusionADMR mediates the stimulatory effects of AM on cancer cells and on endothelial and stellate cells within the tumor microenvironment. These data support the further development of ADMR as a useful target treatment of pancreatic cancer.

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Section: Discussionmentioning

confidence: 47%

The ADMR Receptor Mediates the Effects of Adrenomedullin on Pancreatic Cancer Cells and on Cells of the Tumor Microenvironment

et al. 2009

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“…Therefore, the age-related decrease in AM and its mRNA levels in ventral prostate may be due to the reduction of circulating testosterone concentrations. It has been demonstrated that AM causes a relaxation of the smooth muscle in the rat prostate (30) and increases prostatic blood flow (31); therefore, reduction of AM with age may affect the secretion and motility of the gland. As in the testis, the change in the gene expression of the receptor component proteins was mainly in RAMP1, suggesting a possible decrease in binding and response to CGRP, although there was also a slight decrease in CRLR gene expression.…”

Section: Discussionmentioning

confidence: 99%

Effect of Aging on the Expression of Adrenomedullin and Its Receptor Component Proteins in the Male Reproductive System of the Rat

Li¹,

Wai‐Sum²,

Tang³

2007

The Journals of Gerontology Series A: Biological Sciences and M

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This study investigated the levels of adrenomedullin (AM) and the gene expression of AM, calcitonin receptor-like receptor (CRLR), receptor activity-modifying proteins (RAMPs), and receptor-coupling protein (RCP) in the testis, ventral prostate, seminal vesicle, and epididymis in rats aged 3, 12, and 20 months by radioimmunoassay and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). The results indicate an age-related increase in AM and its messenger RNA (mRNA) levels in the testis and decrease in the sex accessory glands. The gene expression of CRLR and RCP decreased only in the sex accessory glands. The changes in the gene expression of RAMPs suggest that the major increase was in CGRP receptors in the testis, whereas the major decreases in the ventral prostate and the seminal vesicles might be CGRP and AM receptors, respectively. The decreases in these receptors were similar in the epididymis. The results suggest possible roles of AM in the male reproductive system during aging.

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“…Marinoni et al [2007] have suggested that the prostate is the major source of seminal fluid ADM in the human. ADM in the prostate may increase blood flow [Shibata et al 2006], and decrease the smooth muscle contraction [Ventura et al 2000], leading to an accumulation of fluid inside the gland. Our results show that much of the ADM in the coagulating gland is secreted while relatively little is secreted from the seminal vesicle.…”

Section: Discussionmentioning

confidence: 99%

Possible functions of adrenomedullin from the seminal fluid in the female reproductive tract of the rat

Liao

Kong²,

Tang³

et al. 2012

Systems Biology in Reproductive Medicine

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Adrenomedullin (ADM) is found in male accessory sex glands and is part of the seminal secretion. It plays an important role in protecting the sperm in the female reproductive tract. In this study, we investigated the roles of ADM in inflammation and oxidative stress in the endometrium and in leukocyte and macrophage infiltration in the endometrial stroma. The expression of the ADM gene in the ventral prostate, coagulating gland, and seminal vesicle was determined by real time PCR. The peptide levels in the tissue and secretion were measured using an EIA Kit. The highest ADM mRNA and peptide levels were found in the ventral prostate. Most of the ADM in the seminal vesicle was stored in the tissue while little was secreted. The expression of the IL-1β gene and the secretion of TNFα and IL-6 in uterine tissue decreased significantly after treatment with ADM for 4 hours. Using an immunostaining method, the levels of leukocyte and macrophage infiltration were found to be lower at 24 hours post coitus than 1.5 hours post coitus. The infusion of ADM receptor antagonist reduced the infiltration of leukocyte and macrophages in the endometrial stroma at 24 hours post coitus. As to the anti-oxidative effect of ADM in the female tract, the reactive oxygen species (ROS) level in isolated endometrial epithelial cells was significantly decreased after treatment with ADM or seminal fluid. Our findings demonstrated that ADM in the seminal secretion may modify the inflammatory responses, play an anti-oxidative role, and increase leukocyte and macrophage infiltration in the uterus.

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Participation of adrenomedullin and its relation with vascular endothelial growth factor in androgen regulation of prostatic blood flow in vivo

Cited by 6 publications

References 33 publications

The ADMR Receptor Mediates the Effects of Adrenomedullin on Pancreatic Cancer Cells and on Cells of the Tumor Microenvironment

The ADMR Receptor Mediates the Effects of Adrenomedullin on Pancreatic Cancer Cells and on Cells of the Tumor Microenvironment

Effect of Aging on the Expression of Adrenomedullin and Its Receptor Component Proteins in the Male Reproductive System of the Rat

Possible functions of adrenomedullin from the seminal fluid in the female reproductive tract of the rat

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