title: 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.
abstract: 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.
authors.affiliation: Departments of Paediatrics and Neurosurgery, University of Erlangen-Nuremberg, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Knerr
authors.forename: S
authors.initials: S
authors.lastname: Schuster
authors.forename: P
authors.initials: P
authors.lastname: Nomikos
authors.forename: M
authors.initials: M
authors.lastname: Buchfelder
authors.forename: J
authors.initials: J
authors.lastname: Dötsch
authors.forename: E
authors.initials: E
authors.lastname: Schoof
authors.forename: R
authors.initials: R
authors.lastname: Fahlbusch
authors.forename: W
authors.initials: W
authors.lastname: Rascher
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D053607:Adrenomedullin; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D020738:Leptin / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009478:Neuropeptide Y / Q000235:genetics; D009479:Neuropeptides / Q000235:genetics*; D010455:Peptides / Q000235:genetics; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism; D058265:Receptors, Adrenomedullin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D018000:Receptors, Peptide / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D006728:Hormones; C515448:LEPR protein, human; D020738:Leptin; D009478:Neuropeptide Y; D009479:Neuropeptides; D010455:Peptides; D058265:Receptors, Adrenomedullin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D018000:Receptors, Peptide; D053607:Adrenomedullin