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.

Quantitative analysis of a panel of gene expression in prostate cancer—with emphasis on NPY expression analysis

“…Another study found lower degrees of proNPY processing to NPY in tumor tissue were correlated to advanced clinical stages and poor outcome in neuroblastomas (Bjellerup et al, 2000). However, Knerr et al(2001) investigated a series of intracranial tumors and demonstrated that well-differentiated tumors (such as grade I astrocytomas) exhibit higher levels of NPY than anaplastic tumors. The importance of NPY in the prostate carcinoma is rarely investigated.…”

Maturation of the expression of adrenomedullin, endothelin-1 and nitric oxide synthases in adipose tissues from childhood to adulthood

“…3,5,6 ADM gene expression and peptide production could be demonstrated in many types of normal and also in neoplastic cells. [7][8][9][10] ADM binding sites are also found in various tissues; a shared receptor with calcitonin gene-related peptide (CGRP) could be characterized further as being regulated by specific receptor activity modifying proteins (RAMPS). 11 ET-1 stimulates ADM expression in vascular smooth muscle cells (VSMC) as do the inflammatory cytokines, but the regulation profiles of these vasoactive substances are rather complex.…”

The role of leptin in the regulation of TSH secretion in the fed state: in vivo and in vitro studies

“…The local synthesis of leptin is supported by the presence of leptin mRNA, in rat and mouse pituitaries, and in human pituitary adenomas (Morash et al 1999, Jim et al 2000, Knerr et al 2001, Korbonits et al 2001. Additionally, in rat and mouse pituitaries, thyrotrophs and other pituitary cells express leptin and leptin receptors (Morash et al 1999, Jim et al 2000, Korbonits et al 2001, Knerr et al 2001.…”

“…The detection of leptin receptor in the human (Jim et al 1999, Knerr et al 2001, Korbonits et al 2001 and rat (Jim et al 2000, Sone et al 2001 pituitary gland raises the possibility that circulating leptin might also act directly to modulate TSH release. It has been shown that leptin regulates secretion of other pituitary hormones from isolated glands or cell cultures (Casanueva & Dieguez 1999).…”